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Abstract

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, antioxidant, antiemetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and antioxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9) -tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9) -tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

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... Cannabidiol (CBD), another compound of the cannabis plant, is a non-addictive substance that can be used for pharmacotherapy [13]. It has antiemetic, analgesic, anti-inflammatory, antioxidant, antidepressant, anxiolytic, immunomodulatory and neuroprotective effects [6,7,[14][15][16]. The anti-inflammatory effects of CBD are manifested by reducing the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6) and regulating inflammatory processes [16]. ...
... It has antiemetic, analgesic, anti-inflammatory, antioxidant, antidepressant, anxiolytic, immunomodulatory and neuroprotective effects [6,7,[14][15][16]. The anti-inflammatory effects of CBD are manifested by reducing the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6) and regulating inflammatory processes [16]. Additionally, CBD inhibits Toll-like receptor (TLR) signalling pathways, suppressing macrophage activity and reducing inflammatory responses [17]. ...
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Current chelation treatments used for cadmium poisoning may cause some serious side effects. Thus, safer novel treatments could be promising for clinical use. This study evaluated the effects of cannabidiol on Cd toxicity. Four groups of 10 mice were formed: Groups I and III were cadmium‐free, while groups II and IV received 50 mg/L cadmium in drinking water. Groups III and IV received daily cannabidiol (25 mg/kg) via intragastric gavage. After 30 days, the animals were killed, and blood and tissue samples were collected. Oxidative stress and inflammation markers, including glutathione, catalase, myeloperoxidase, TNF‐α, IL‐1β and IL‐6, were analysed using ELISA. Additionally, histological evaluations of the liver, kidney and testis were performed. Cadmium exposure reduced glutathione and catalase levels in the blood, liver, kidney and testis, while increasing myeloperoxidase. Cannabidiol mitigated these effects on oxidative stress markers. Cannabidiol also reduced the increase in proinflammatory cytokines. Histopathological analysis revealed reduced liver and kidney damage in cannabidiol‐treated groups compared to cadmium‐only groups. In addition, histopathological evaluation showed CBD had no protective effect on the testicular tissue against Cd toxicity. Our results indicate that cannabidiol protects against some toxic effects of cadmium. If confirmed by future studies, cannabidiol may be proposed as a novel treatment for cadmium toxicity.
... CBD has been studied extensively in preclinical investigations for a variety of neurodegenerative disorders [70]. The neuroprotective properties of CBD do not appear to depend on the direct activation of CB1 receptors [71], even though CB2 receptor involvement has been documented in specific pathological conditions [72]. The direct activity of CBD at these CBRs is still under debate. ...
... The positive impact of CBD on the quality of life of PD patients may be due to its therapeutic effects on non-motor symptoms. CBD differs from traditional drugs, which usually target specific sites of action to treat specific conditions by acting on a broader range of conditions simultaneously and through different yet unidentified mechanisms of action [71,129]. The multi-target properties of CBD may make it more useful than other drugs for people with PD, as the pathophysiology of PD (and other disorders) is generally multifactorial. ...
Article
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Background Parkinson’s disease (PD) is primarily known as a motor disorder; however, its debilitating non-motor symptoms have a significant impact on patients’ quality of life. The current standard treatment, l-DOPA, is used to relieve motor symptoms, but prolonged use is often associated with severe side effects. This creates an urgent need for effective alternatives targeting both motor and non-motor symptoms. Objectives Over the past decade, Cannabis sativa and its cannabinoids have been widely studied across various health conditions. Among these compounds, cannabidiol (CBD), a non-psychoactive component, is garnering growing interest due to its multi-targeted pleiotropic properties. This work aims to provide a comprehensive overview of CBD’s efficacy in PD. Methods This review compiles data on both motor and non-motor symptoms of PD, integrating results from preclinical animal studies and available clinical trials. Results Preclinical research has demonstrated promising results regarding CBD’s potential benefits in PD; however, the total number of clinical trials is limited (with only seven studies to date), making it difficult to draw definitive conclusions on its efficacy. Conclusions While preclinical findings suggest that CBD may have therapeutic potential in PD, the limited number of clinical trials highlights the need for further research. This review emphasizes the gaps that need to be addressed in future studies to fully understand CBD’s role in treating both motor and non-motor symptoms of PD.
... Additionally, the optimal dosages, formulations, and long-term effects of CBD require further investigation. It is crucial for individuals considering CBD as a treatment option for neurological disorders to consult with their healthcare professionals [18]. They can provide personalized advice, weigh the potential benefits and risks, and ensure that CBD does not interact with any other medications the individual may be taking [19]. ...
... Review CBD showed potential in neurodegenerative disorders [18] Please note that this table is for illustrative purposes only, and the specific details and outcomes of each study may vary. It is important to consult the original studies for a more comprehensive understanding of the research conducted on each neurological disorder. ...
Article
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Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's disease, which present major healthcare concerns on a worldwide scale. Despite the lack of available therapies, CBD has been shown to possess a variety of pharmacological effects in preclinical and clinical studies, making it an intriguing competitor. This review brings together the most recent findings on the endocannabinoid and neurotransmitter systems, as well as anti-inflammatory pathways, that underlie CBD's modes of action. Synthesized efficacy and safety assessments for a range of neurological illnesses are included, covering human trials, in vitro studies, and animal models. The investigation includes how CBD could protect neurons, control neuroinflammation, fend off oxidative stress, and manage neuronal excitability. This study emphasizes existing clinical studies and future possibilities in CBD research, addressing research issues such as regulatory complications and contradicting results, and advocates for further investigation of therapeutic efficacy and ideal dose methodologies. By emphasizing CBD's potential to improve patient well-being, this investigation presents a revised viewpoint on its suitability as a therapeutic intervention for neurological illnesses.
... Previous reports showed that CBD may have therapeutic benefits. In fact, this compound has proven to have antinflammatory [12][13][14][15][16], neuroprotective [17][18][19][20][21][22][23][24][25][26][27][28][29], anxiolytic [20,30], analgesic [31], antidepressant [32], hepatoprotective [33] and immunomodulator effects [34][35][36]. In the following years, CBD has been studied to determine its antioxidant efficacy in different quantum chemical and mechanical methods [11], in vitro models of neurodegenerative diseases [22,[37][38][39][40][41][42], and a few in vivo models in CNS with promising results [33,[43][44][45]. ...
... It is considered that there are seven mechanisms through which neuroprotection is achieved: antiapoptosis, antinflamatory responses, blocking of glutamate-mediated toxicity, trophic factors, blocking of aggregating proteins, antioxidant mechanisms and other miscellaneous [67]. Different studies offer solid proof of the neuroprotective properties of CBD [11,17,19,[20][21][22][23]27]. Two main studies have evaluated the CBD neuroprotective mechanism through antioxidation in the central nervous systems in vivo. ...
Article
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Pharmacological and therapeutic properties of phytocannabinoids present in Cannabis sativa L. (Linnaeus) are of increasing interest worldwide. In the present study, a group of goldfish (Carassius auratus) were used to test the antioxidant effects of cannabidiol (CBD) in the brain of in vivo chlorpyrifos (CPF)-exposed fish. CPF, an organophosphate insecticide, is known for its pro-oxidant effects and irreversible inhibition on cholinesterase (ChE) enzymes. The experimental fish (n=22) (22.86 ± 1.15 g body weight, 8.33 ± 0.16 cm total length) were randomly distributed in 4 different treatments: A. Control fish (n=6), B. CPF-exposed fish (n=5), C. CPF-exposed + IP injected vehicle (n=5), and D. CPF-exposed + IP-injected CBD (5 mg/Kg) (n=6). Fish were humanely sacrificed after 96 h of the experimental time and brains were processed to measure F2-isoprostanes (F2-IsoPs) as a biomarker of oxidative stress response (ELISA OxiSelect™ 8-iso-PGF2a). ChE activity was measured in fish blood plasma as a biomarker of CPF exposure. Mean values of F2-IsoPs and ChE were used as statistics for comparison among treatments. Neither of the fish treatments showed signs of acute poisoning after the CPF exposure. However, plasma ChE activity showed inhibition effects in the corresponding groups after the 96-h exposure to CPF. The lowest F2-IsoPs value (mean ± SE, pg/ml) was found in the CPF-exposed + CBD-injected fish (281 ± 45) followed by the controls (396 ± 90). The two highest values of F2-isoprostanes were present in the CPF-exposed (728 ± 236) and the CPF-exposed + vehicle-injected fish (566 ± 90) (ANOVA, 95%, p <0.05; Fisher least significant difference). Three types of functional groups within the CBD structure are considered a key factor to explain the prevention of oxidative stress: limonene, phenol and aliphatic group. These groups, particularly the phenol, transfer electrons and hydrogen atoms to avoid the lipid peroxidation in the tissues affected by pro-oxidant agents. Results in the present work showed that CBD protected of the oxidative stress caused by CPF in the brain of goldfish. This neuroprotective action of CBD against oxidative stress promotes further research to explore pharmacological and therapeutic applications.
... Several studies reported that CBD can promote neurogenesis, improve memory, and enhance focus. Additionally, some authors showed that CBD may be neuroprotective, based on its antioxidant and anti-inflammatory properties, suggesting that it could afford protection against numerous neuropathological disorders (reviewed in [168][169][170]). ...
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Background: Cannabidiol (CBD) is a cannabinoid present in the hemp plant (Cannabis sativa L.). Non-medicinal CBD oils with typically 5–40% CBD are advertised for various alleged positive health effects. While such foodstuffs containing cannabinoids are covered by the Novel Food Regulation in the European Union (EU), none of these products have yet been authorized. Nevertheless, they continue to be available on the European market. Methods: The Permanent Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) reviewed the currently available data on adverse and potential beneficial effects of CBD in the dose range relevant for foods. Results: Increased liver enzyme activities were observed in healthy volunteers following administration of 4.3 mg CBD/kg bw/day and higher for 3–4 weeks. As lower doses were not tested, a no observed adverse effect level (NOAEL) could not be derived, and the dose of 4.3 mg/kg bw/day was identified as the lowest observed adverse effect level (LOAEL). Based on the CBD content and dose recommendations of CBD products on the market, the SKLM considered several exposure scenarios and concluded that the LOAEL for liver toxicity may be easily reached, e.g., via consumption of 30 drops of an oil containing 20% CBD, or even exceeded. A critical evaluation of the available data on potential beneficial health effects of CBD in the dose range at or below the LOAEL of 4.3 mg/kg bw/day revealed no scientific evidence that would substantiate health claims, e.g., in relation to physical performance, the cardiovascular, immune, and nervous system, anxiety, relaxation, stress, sleep, pain, or menstrual health. Conclusions: The SKLM concluded that consumption of CBD-containing foods/food supplements may not provide substantiated health benefits and may even pose a health risk to consumers.
... HSC is rich in natural polyphenols such as tocopherol and cannabidiol, which are known for their antioxidant properties (Jiang et al., 2001). Cannabidiol also has anti-inflammatory effects (Fernandez-Ruiz et al., 2013). This is evidenced by the decrease of proinflammatory cytokines in serum in the present study (Table 9). ...
Article
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Hemp seed cake (HSC) (Cannabis sativa L.) is a high-quality plant-derived protein source rich in polyunsaturated fatty acid (PUFA). To assess the effects of HSC addition in diets on the growth and meat quality in broiler chicken, a total of 240 female three-yellow chickens (50 days of age) were randomly assigned to four groups and fed with varying levels of HSC (0% (HSC0), 5% (HSC5), 10% (HSC10), and 20% (HSC20)) for 9 weeks. As a result, the daily feed intake, weight gain and feed conversion efficiency were significantly increased in the HSC20 group. Moreover, the meat quality traits, including the meat colour, water-holding capacity, intramuscular fat content, and proportion of n-3 PUFA significantly improved, and the expression of lipid synthesis genes, were increased in the HSC20 group. Meanwhile, the development of immune organs and the anti-inflammatory capabilities were enhanced in the HSC20 group. In addition, the blood lipid of chicken was reduced by improving the lipid metabolism in the HSC20 group. Therefore, adding 20% HSC in the feed had a notable effect on the growth, antioxidant and immune capabilities, blood lipid metabolism, and meat performance of the female three-yellow chickens. These findings provide significant information for improving the production performance of broiler chickens through the effective utilization of HSC.
... A number of authors have evaluated the efficacy of cannabinoidbased therapies with the presence of CBD or THC to reduce pain, focusing on the management of chronic and neuropathic pain associated with cancer patients [17,50,[55][56][57][58][59][60][61][62]. ...
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El presente estudio tiene como objetivo dar a conocer la composición química y el posible potencial medicinal de variedades de cannabis no psicoactivo cultivadas en el departamento del Cauca. Los cannabinoides fueron identificados y cuantificados por cromatografía líquida de alta resolución acoplada a un detector ultravioleta (HPLC/UV) para el análisis de la flor, y cromatografía de gases acoplada a un espectrómetro de masas (GC-MS) para el análisis de los extractos etanólicos y contenido terpenos. Los fenoles se cuantificaron por reacción con el reactivo de Folin & Ciocalteau; para la determinación de flavonoides y antraquinonas, los extractos fueron tratados con AlCl3. Finalmente, para determinar la actividad antioxidante se utilizaron tres métodos: DPPH, ABTS y FRAP. Se pudo determinar que las variedades A y B contenían porcentajes de tetrahidrocannabinol total (THC) menores al 1% y porcentajes de cannabidiol total (CBD) entre 9-15%. En los extractos etanólicos se alcanzaron concentraciones (m/m) de CBD en las variedades A y B, del 10% y 13,7%, respectivamente. Se identificaron y cuantificaron nueve terpenos de la muestra A y siete de la muestra B, siendo el β-cariofileno el más abundante en ambos. Teniendo en cuenta que existe evidencia en la literatura de que la relación CBD/THC influye en la actividad biológica, se espera que los extractos etanólicos de las variedades A y B tengan una actividad antioxidante de moderada a baja, lo que, según algunos investigadores, puede estar asociado con el efecto neuroprotector, que puede verse favorecido por la presencia de β-cariofileno.
... Alzheimer's disease (AD) is a form of dementia characterized by neurodegenerative disorders, including the accumulation of amyloid-b, oxidative stress, and neuroinflammation (Tönnies and Trushina 2017;Breijyeh and Karaman 2020). CBD is known for its antioxidant, neuroprotective, and anti-inflammatory properties (Fernández-Ruiz et al. 2013;Atalay et al. 2020). Researchers have demonstrated CBD's ability to reduce reactive gliosis and the neuroinflammatory response while promoting neurogenesis. ...
Article
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Cannabis sativa, the debatable plant, contains a vast array of phytocannabinoids, with a significant presence of cannabidiol. This cannabinoid possesses numerous medicinal properties, with its analgesic capabilities being one of the earliest subjects of study. While the exact mechanism of how CBD works remains somewhat unclear, its mode of action varies depending on the route of administration, including oral, sublingual, rectal, transdermal, and inhalation. Despite CB’s versatility in addressing various symptoms through multiple administration methods, a noteworthy challenge lies in its limited absorption and bioavailability. The compound's high lipophilicity and low water solubility contribute to its suboptimal bioavailability. To address this issue, extensive research has explored CBD-loaded nanoformulations, encompassing nanomicelles, nanoparticles, SNEDDS (self-nanoemulsifying drug delivery systems), liposomes, and pro-nano-lipospheres. Both preclinical and clinical studies are underway at a substantial pace to establish the safety and efficacy of this cannabinoid. Some CBD nanoformulations have even met FDA regulations and are available in the market. CBD's multifaceted nature, with its potential application against various diseases, has captivated researchers, leading to an increased interest in this compound. This heightened interest has resulted in the filing of numerous patents worldwide. Additionally, research has demonstrated CBD's effects on conditions such as Parkinson's disease, epilepsy, multiple sclerosis, Huntington's disease, Alzheimer's disease, various cancers, pain, and inflammation, which will be discussed in the concluding section of this article.
... NADPH oxidase, responsible for the production of Reactive Oxygen Species (ROS), plays a significant role in mitigating adverse aspects of neurodegenerative diseases. 27 CBD's ability to attenuate microglial cell activation is also associated with mechanisms involving FAAH inhibition, 28 PPAR-γ, 29 and 5-HT1a receptors 30,31 in innate cells and lymphocytes. 32 CBD, on the other hand, has a central role in regulating the TRPV1, PPAR and 5-HT1A receptors and acts as an antagonist for the GPR55 receptor. ...
Article
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Cannabis sativa, commonly known as marijuana, has been historically used for medicinal and recreational purposes. It has been employed in the treatment of neurological conditions. Cannabidiol (CBD), the active component of cannabis, has shown therapeutic effects and has been studied extensively for its potential benefits in various neurological disorders using preclinical models. The objective of this review is to consolidate current research on CBD and its association with Apo-lipoprotein (ApoE) and other targets related to neurodegenerative diseases. A comprehensive search of the PubMed Scopus and google scholar databases was conducted using keywords such as CBD, Microglia activation, astrocytes, ApoE, mammalian target of Rapamycin and wingless-related integration site expression. The available evidence suggests that CBD does not significantly affect the endocannabinoid system, except in vitro at high concentrations, thereby generating considerable interest in its therapeutic potential. However, the current physiological targets for CBD are challenging to exploit for neurological treatment, leading to uncertain clinical findings. In certain cases, there is minimal or no correlation between the disease and the identified targets. This review examines the classic receptors, neurotransmitters and pathways associated with both ApoE and CBD. Additionally, several interconnected targets of CBD have been discovered that exhibit a relationship with a specific ApoE, rather than merely triggering its action. Various molecular targets of CBD have been identified for specific neurodegenerative diseases, playing a central role in the ApoE system.
... Consequently, CBD is beneficial in treating conditions like arthritis, endometriosis, multiple sclerosis, and fibromyalgia [37]. Additionally, CBD exhibits neuroprotective effects, preventing neuronal damage induced by chronic diseases [38]. Its potent anti-inflammatory properties contribute to the treatment of inflammation by blocking the activation of cytokines and chemokines, which are the primary proteins responsible for inflammatory responses in the body [39]. ...
Article
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Cannabis, traditionally used for recreation due to psychoactive compounds in its leaves, flowers, and seeds, has not been thoroughly explored for potential therapeutic benefits. Δ9- trans -Tetrahydrocannabinol, a key cannabinoid in cannabis, causes hallucinogenic effects and delirium symptoms. In contrast, cannabidiol (CBD) does not induce hallucinations and has shown effectiveness in treating symptoms of various rare, incurable diseases. Cannabis exhibits neuroprotective, anti-inflammatory, anti-thrombotic, anti-bacterial, analgesic, and antiepileptic properties, recently attracting more attention. This review aims to summarize comprehensively the impact of cannabis on human health, focusing on endocannabinoids and their receptors. It also delves into recent CBD research advancements, highlighting the compound’s potential medical applications. Overall, this paper provides valuable insights into the prospective development of medical cannabis, with a particular emphasis on CBD.
... The alleged effectiveness of this chemical, along with other cannabinoids like delta-9-tetrahydrocannabinol (THC), in the treatment of several medical conditions has led to its rise in popularity. Moreover, CBD has been reported to be an antidote to certain disorders such as Parkinson's disease, and seizures/epilepsy without exerting psychotropic effects, unlike THC, which is associated with psychoactive consequences (Fernández-Ruiz et al. 2013;Porter et al. 2021). ...
Article
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Background The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed. Main body This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion. Conclusion CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD’s therapeutic tendencies in neurological/neuropsychiatric disorders.
... The market size is projected to be in excess of USD 108.8 billion by 2027 (Ugalmugle and Swain, 2020). A significant growth area within the cannabinoid market is the production of purified compounds, as some cannabinoids find application within the medical industry (Fernández-Ruiz et al., 2013;Pisanti et al., 2017). Cannabinoid isolates has been found to treat or ease symptoms of pain, anxiety, loss of appetite, insomnia, and nausea (Small, 2016). ...
... CBD has less psychoactive effects. It possesses antiemetic, analgesic, anti-in ammatory, antioxidant, antidepressant, anxiolytic, immunmodulatory, and neuroprotective effects [11,[14][15][16][17]. Two separate animal studies have demonstrated that CBD reduced the cobalt-triggered epileptic seizures, indicating that it may have a protective effect against seizures induced by toxic metals [18,19]. ...
Preprint
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Purpose Considering the significant toxicity caused lead (Pb), identifying substances that can prevent or alleviate the toxic effects of Pb is important. This study aims to evaluate the protective effects of an anti-inflammatory, antioxidant substance; cannabidiol (CBD) against Pb toxicity. Methods A total of 4 groups, each consisting 10 mice were used. Groups I and III were not exposed to Pb, while Pb exposure was induced in groups II and IV by adding 1 gr/L of Pb to the drinking water. CBD was administered daily via intragastric gavage at a 25 mg/kg dose in groups III and IV. At the end of 30 days, the mice were euthanized, and blood and liver, kidney, testis tissue samples were collected. Levels of oxidative stress markers GSH, CAT, MPO, and pro-inflammatory cytokines TNF-α, IL-1β, IL-6 were measured using ELISA kits. Histological evaluation of the tissues samples was performed. Results Comparison between groups II and IV showed that CBD alleviated the oxidant and inflammatory damage caused by Pb as blood CAT, GSH levels increased and MPO, TNF- α, IL-1β, IL-6 levels decreased in CBD administered, Pb intoxicated mice compared to only Pb intoxicated mice. CBD also decreased the toxic effects of Pb in liver, kidney and testis tissues (p < 0.0001 for most comparisons). Comparison between groups III and IV revealed similar results as it showed that Pb reduced the beneficial effects of CBD. Conclusion This study showed that CBD has a protective effect against Pb toxicity. This finding indicates that CBD could be used as a food additive or supportive treatment for alleviating the toxic effects of Pb at risked population groups.
... Cannabidiol, a component of the Cannabis sativa glandular hairs, reported having anticonvulsive, hypnotic, sedative, antinausea, antipsychotic, antiinflammatory, antioxidant, antiapoptotic, and antihyperalgesic neuroprotective properties (Mechoulam et al., 2002). Cannabidiol has been suggested to have neuroprotective effects in neurodegenerative diseases, including PD, AD, epilepsy, and MS (Fernández-Ruiz et al., 2013;Cassano et al., 2020). Cannabidiol has been reported to stimulate cell survival, attenuate ROS, nitrative stress, lipid peroxidation, iNOS expression, improve mitochondrial biogenesis, and function in a concentrationdependent manner (Cassano et al., 2020). ...
... A list of potential receptor targets of CBD was provided in a 2015 review paper in which the A 2A R was not included [16]. Effects of CBD, mainly beneficial, have been described in epilepsy, inflammation (including neuroinflammation), pain, malignancies and psychosis [17][18][19][20][21][22][23][24][25][26][27][28][29][30]. ...
Article
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Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A2A receptor agonist, CGS 21680, on Gs-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A2A receptor.
... THC, similar to AEA, is a partial agonist at CB1 receptors. 32,33 CBD is a negative allosteric modulator of CB1 and has been shown to enhance AEA levels indirectly. 34-36 CBD may also modulate gamma-aminobutyric acid (GABA) activity, a neurotransmitter responsible for the inhibition of neuronal excitability, increasing dopamine production. ...
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Aim This study aims to analyze the health‐related quality of life (HRQoL) and safety outcomes in attention‐deficit/hyperactivity disorder (ADHD) patients treated with cannabis‐based medicinal products (CBMPs). Methods Patients were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the following patient‐reported outcome measures (PROMs) at 1, 3, 6, and 12 months from baseline: EQ‐5D‐5L index value, generalized anxiety disorder‐7 (GAD‐7) questionnaire, and the single‐item sleep quality score (SQS). Secondary outcomes assessed the incidence of adverse events. Statistical significance was defined as p < 0.050. Results Sixty‐eight patients met the inclusion criteria. Significant improvements were identified in general HRQoL assessed by EQ‐5D‐5L index value at 1, 3, and 6 months ( p < 0.050). Improvements were also identified in GAD‐7 and SQS scores at 1, 3, 6, and 12 months ( p < 0.010). 61 (89.71%) adverse events were recorded by 11 (16.18%) participants, of which most were moderate ( n = 26, 38.24%). Conclusion An association between CBMP treatment and improvements in anxiety, sleep quality, and general HRQoL was observed in patients with ADHD. Treatment was well tolerated at 12 months. Results must be interpreted with caution as a causative effect cannot be proven. These results, however, do provide additional support for future evaluation within randomized controlled trials.
... Effective strategies for the treatment of PD include normalizing glutamate homeostasis, reducing oxidative stress, and attenuating glial activation (Martin-Moreno et al., 2011;Fernandez-Ruiz et al., 2013;Bhunia et al., 2022). During PD, the mitochondrial Ca 2+buffering system in substantia nigra neurons was shown to be impaired and led to Ca 2+ -induced excitotoxicity (Hoye et al., 2008;Hurley et al., 2013). ...
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Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.
... Cannabinoids are related to 5-HT receptors due to interactions of CBD and 5-HT 1A , what results in attenuated diabetic neuropathy in animal models (Jesus et al., 2019). CBD is a partial agonist of 5HT 2A and antagonist of 5HT 3A receptors (Fernández-Ruiz et al., 2013;Soares and Campos, 2017;Meissner and Cascella, 2022;). The potential benefits of these interactions to pain management, however, are still unclear. ...
... As for 5HT 1A , they are serotonin receptors coupled to a Gi/o protein and have been related to cannabinoids, including neuroprotective effects [66]. These receptors are considered autosomal and are located on presynaptic membranes and are also found postsynaptically in various areas of the brain [67]. ...
Preprint
Neurodegenerative diseases have complex etiologies, however, neuroinflammation and oxidative stress are important markers in this pathogenesis and, in this sense, cannabinoids, especially CBD, have been identified as potential therapeutics for playing a neuroprotective role. Studies have demonstrated the neuroprotective effect of cannabinoids and derivatives of Cannabis sativa L in diseases of the central nervous system due to their interaction with the endocannabinoid system through receptors and other molecular targets. The aim of this review was to provide an overview of the endocannabinoid system and a summary of the clinical and preclinical findings of the therapeutic use of cannabinoids in epilepsy, multiple sclerosis and Parkinson’s disease, pointing out interactions with molecular targets and the potential for neuroprotection of CBD. Electronic searches were carried out in international databases, including studies that presented consistent data on this subject. Significant therapeutic effects of CBD were shown for epilepsy and Parkinson’s disease, while nabiximols contributed to the reduction of spasticity, being a frequent option for the treatment of multiple sclerosis. Although much has been projected on the therapeutic potential of cannabinoids for neurological disorders, there is a long way to go in the search for strong scientific evidence of their pharmacological effectiveness.
... The chemistry and pharmacology of CBD, as well as various molecular targets including CBD receptors and other CBD-interactive components of the endocannabinoid system, have been reviewed extensively [4][5][6][7]. The preliminary results of many studies have prompted the exploration of the therapeutic potential of CBD in relation to various diseases, particularly cancer and drug-resistant epilepsy [7][8][9][10][11][12]. ...
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The increasing legalization of Cannabis sativa plant products has sparked growing interest in their therapeutic applications. Prohibition laws established in 1937 hindered formal research on cannabis, a plant with cultural and medicinal roots dating back to 2700 BC in Chinese history. Despite regulatory hurdles, published research on cannabis has emerged; yet elite athletes remain an underrepresented population in these studies. Athletes, known for exploring diverse substances to optimize performance, are drawn to the potential benefits of cannabinoid therapy, with anecdotal reports suggesting positive effects on issues ranging from anxiety to brain injuries. This review aims to evaluate empirical published cannabis research with a specific focus on its potential applications in athletics. The changing legal landscape, especially the removal of cannabis from drug testing programs in leagues such as the National Basketball Association (NBA), and endorsements by Major League Baseball (MLB) for cannabinoid products and the National Football League (NFL) for cannabis research, reflects a shift in the acceptability of such substances in sports. However, stigma, confusion, and a lack of education persist, hindering a cohesive understanding among sports organizations, including business professionals, policymakers, coaches, and medical/training staff, in addition to athletes themselves. Adding to the confusion is the lack of consistency with cannabinoid regulations from sport to sport, within or out of competition, and with cannabis bioactive compounds. The need for this review is underscored by the evolving attitudes toward cannabinoids in professional sports and the potential therapeutic benefits or harms they may offer. By synthesizing current cannabis research, this review aims to provide a comprehensive understanding of the applications and implications of cannabinoid use in the realm of athletics.
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The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ(9)tetrahydrocannabivarin (Δ(9)-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ(9)-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ(9)-THC pCB-based medicines.
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We have investigated whether a 1:1 combination of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation. We monitored the extent of this damage and the possible preservation of the striatal parenchyma by treatment with a Sativex-like combination of phytocannabinoids using different histological and biochemical markers. Results were as follows: (i) malonate increased the volume of edema measured by in vivo NMR imaging and the Sativex-like combination of phytocannabinoids partially reduced this increase; (ii) malonate reduced the number of Nissl-stained cells, while enhancing the number of degenerating cells stained with FluoroJade-B, and the Sativex-like combination of phytocannabinoids reversed both effects; (iii) malonate caused a strong glial activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both responses; and (iv) malonate increased the expression of inducible nitric oxide synthase and the neurotrophin IGF-1, and both responses were attenuated after the treatment with the Sativex-like combination of phytocannabinoids. We also wanted to establish whether targets within the endocannabinoid system (i.e., CB(1) and CB(2) receptors) are involved in the beneficial effects induced in this model by the Sativex-like combination of phytocannabinoids. This we did using selective antagonists for both receptor types (i.e., SR141716 and AM630) combined with the Sativex-like phytocannabinoid combination. Our results indicated that the effects of this combination are blocked by these antagonists and hence that they do result from an activation of both CB(1) and CB(2) receptors. In summary, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying signs of disease progression in a proinflammatory model of HD, which adds to previous data obtained in models priming oxidative mechanisms of striatal injury. However, the interest here is that, in contrast with these previous data, we have now obtained evidence that both CB(1) and CB(2) receptors appear to be involved in the effects produced by a Sativex-like phytocannabinoid combination, thus stressing the broad-spectrum properties of Sativex that may combine activity at the CB(1) and/or CB(2) receptors with cannabinoid receptor-independent actions.
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Background and purpose: Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid of psychoactive activity, are, potentially, safe and effective alternatives for alleviating neuroinflammation and neurodegeneration. Experimental approach: We used experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) in C57BL/6 mice, as a model of multiple sclerosis. Using immunocytochemistry and cell proliferation assays we evaluated the effects of CBD on microglial activation in MOG-immunized animals and on MOG-specific T-cell proliferation. Key results: Treatment with CBD during disease onset ameliorated the severity of the clinical signs of EAE. This effect of CBD was accompanied by diminished axonal damage and inflammation as well as microglial activation and T-cell recruitment in the spinal cord of MOG-injected mice. Moreover, CBD inhibited MOG-induced T-cell proliferation in vitro at both low and high concentrations of the myelin antigen. This effect was not mediated via the known cannabinoid CB(1) and CB(2) receptors. Conclusions and implications: CBD, a non-psychoactive cannabinoid, ameliorates clinical signs of EAE in mice, immunized against MOG. Suppression of microglial activity and T-cell proliferation by CBD appeared to contribute to these beneficial effects.
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Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist Δ9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both a-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
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(−)-Cannabidiol (CBD) is a non-psychotropic component of Cannabis with possible therapeutic use as an anti-inflammatory drug. Little is known on the possible molecular targets of this compound. We investigated whether CBD and some of its derivatives interact with vanilloid receptor type 1 (VR1), the receptor for capsaicin, or with proteins that inactivate the endogenous cannabinoid, anandamide (AEA). CBD and its enantiomer, (+)-CBD, together with seven analogues, obtained by exchanging the C-7 methyl group of CBD with a hydroxy-methyl or a carboxyl function and/or the C-5′ pentyl group with a di-methyl-heptyl (DMH) group, were tested on: (a) VR1-mediated increase in cytosolic Ca2+ concentrations in cells over-expressing human VR1; (b) [14C]-AEA uptake by RBL-2H3 cells, which is facilitated by a selective membrane transporter; and (c) [14C]-AEA hydrolysis by rat brain membranes, which is catalysed by the fatty acid amide hydrolase. Both CBD and (+)-CBD, but not the other analogues, stimulated VR1 with EC50=3.2 – 3.5 μM, and with a maximal effect similar in efficacy to that of capsaicin, i.e. 67 – 70% of the effect obtained with ionomycin (4 μM). CBD (10 μM) desensitized VR1 to the action of capsaicin. The effects of maximal doses of the two compounds were not additive. (+)-5′-DMH-CBD and (+)-7-hydroxy-5′-DMH-CBD inhibited [14C]-AEA uptake (IC50=10.0 and 7.0 μM); the (−)-enantiomers were slightly less active (IC50=14.0 and 12.5 μM). CBD and (+)-CBD were also active (IC50=22.0 and 17.0 μM). CBD (IC50=27.5 μM), (+)-CBD (IC50=63.5 μM) and (−)-7-hydroxy-CBD (IC50=34 μM), but not the other analogues (IC50>100 μM), weakly inhibited [14C]-AEA hydrolysis. Only the (+)-isomers exhibited high affinity for CB1 and/or CB2 cannabinoid receptors. These findings suggest that VR1 receptors, or increased levels of endogenous AEA, might mediate some of the pharmacological effects of CBD and its analogues. In view of the facile high yield synthesis, and the weak affinity for CB1 and CB2 receptors, (−)-5′-DMH-CBD represents a valuable candidate for further investigation as inhibitor of AEA uptake and a possible new therapeutic agent. British Journal of Pharmacology (2001) 134, 845–852; doi:10.1038/sj.bjp.0704327
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Biochemical studies on postmortem brains of patients with Parkinson’s disease (PD) have greatly contributed to our understanding of the molecular pathogenesis of this disease. The discovery by 1960 of a dopamine deficiency in the nigro-striatal dopamine region of the PD brain was a landmark in research on PD. At that time we collaborated with Hirotaro Narabayashi and his colleagues in Japan and with Peter Riederer in Germany on the biochemistry of PD by using postmortem brain samples in their brain banks. We found that the activity, mRNA level, and protein content of tyrosine hydroxylase (TH), as well as the levels of the tetrahydrobiopterin (BH4) cofactor of TH and the activity of the BH4-synthesizing enzyme, GTP cyclohydrolase I (GCH1), were markedly decreased in the substantia nigra and striatum in the PD brain. In contrast, the molecular activity (enzyme activity/enzyme protein) of TH was increased, suggesting a compensatory increase in the enzyme activity. The mRNA levels of all four isoforms of human TH (hTHl-hTH4), produced by alternative mRNA splicing, were also markedly decreased. This finding is in contrast to a completely parallel decrease in the activity and protein content of dopamine β-hydroxylase (DBH) without changes in its molecular activity in cerebrospinal fluid (CSF) in PD. We also found that the activities and/or the levels of the mRNA and protein of aromatic L-amino acid decarboxylase (AADC, DOPA decarboxylase), DBH, phenylethanolamine N-methyltransferase (PNMT), which synthesize dopamine, noradrenaline, and adrenaline, respectively, were also decreased in PD brains, indicating that all catecholamine systems were widely impaired in PD brains.
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Inhibitory effects of Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabinol (CBN) on the catalytic activities of human recombinant cytochrome P450 (CYP) 2A6 and CYP2B6 were investigated. Δ9-THC, CBD, and CBN noncompetitively inhibited coumarin 7-hydroxylase activity of recombinant CYP2A6 with the apparent K i values of 28.9, 55.0, and 39.8μM, respectively. On the other hand, Δ9-THC, CBD, and CBN inhibited 7-benzoxyresorufin O-debenzylase activity of recombinant CYP2B6 in a mixed fashion with the K i values of 2.81, 0.694, and 2.55μM, respectively. Because the inhibition of CYP2B6 by CBD was the most potent, investigation was conducted to determine which moiety of the CBD structure was responsible for the inhibition. Olivetol and d-limonene, the partial structure of CBD, inhibited the CYP2B6 activity to some extent. Inhibitory effects of CBD-2′-monomethyl ether and CBD-2′,6′-dimethyl ether attenuated with the number of methylations on the phenolic hydroxyl groups in the resorcinol moiety of CBD. Cannabidivarin, a CBD analogue having a propyl side chain, inhibited the CYP2B6 activity less potently than CBD possessing a pentyl side chain. Therefore, both structures of pentylresorcinol and terpene moieties of CBD were suggested to play important roles in the CYP2B6 inhibition. Δ9-THC, CBD, and CBN showed metabolism-dependent inhibition for CYP2A6 but not for CYP2B6. Furthermore, Δ9-THC and CBN were characterized as mechanism-based inhibitors for CYP2A6. The k inact and K I values of Δ9-THC were 0.0169min−1 and 0.862μM, respectively; the k inact and K I values of CBN were 0.00909min−1 and 1.01μM, respectively. These results indicated that Δ9-THC, CBD, and CBN showed differential inhibition against CYP2A6 and CYP2B6. KeywordsMarijuana–Nicotine–Cannabinoid–CYP2A6–CYP2B6–Differential inhibition
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Huntington’s disease (HD) is one of the most frequently found neurodegenerative disorders. Its main clinical manifestations arc chorea, cognitive impairment and psychiatric disorders. It is an autosomal-dominant disorder with almost complete penetrance. The mutation responsible for HD, unstable expansion of a CAG repcat, is located in the 5′ tcrminal section of the gene (ITJS) that encodes huntingtin protein (Htt). The pathophysiology of HD is not entirely clear. One intriguing characteristic of HD is the special vulnerability of the striatum tomutated Htt, despite similar expression of the mutated protcin in other brain regions. Aggregation of mutated Htt, transcriptional dysregulation, altered energy metabolism, excitotoxicity, impaired axonal transport and altered synaptic transmission culminate in neuronal dysfianction and death. There is currently no way ofpreventing or slowing down the disease progression and death usually occurs at about 20 years after dia
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We hypothesized that the anticancer activity of cannabinoids was linked to induction of phosphatases. The effects of cannabidiol (CBD) and the synthetic cannabinoid WIN-55,212 (WIN) on LNCaP (prostate) and SW480 (colon) cancer cell proliferation were determined by cell counting; apoptosis was determined by cleavage of poly(ADP)ribose polymerase (PARP) and caspase-3 (Western blots); and phosphatase mRNAs were determined by real-time PCR. The role of phosphatases and cannabinoid receptors in mediating CBD- and WIN-induced apoptosis was determined by inhibition and receptor knockdown. CBD and WIN inhibited LNCaP and SW480 cell growth and induced mRNA expression of several phosphatases, and the phosphatase inhibitor sodium orthovanadate significantly inhibited cannabinoid-induced PARP cleavage in both cell lines, whereas only CBD-induced apoptosis was CB1 and CB2 receptor-dependent. Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.
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Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.
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Background and purpose: To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. Experimental approach: The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and to modify the ability of the 5-HT(1A) agonist, 8-OH-DPAT, to stimulate [(35) S]GTPγS binding in rat brainstem membranes. Key results: CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg(-1) , but not 40 mg·kg(-1) )-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose-response curve) at enhancing the ability of 8-OH-DPAT to stimulate [(35) S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping. Conclusions and implications: These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN. Linked articles: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
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