Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 992
Filtrar
1.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576119

RESUMO

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.


Assuntos
Apoptose/efeitos dos fármacos , Canabidiol/farmacologia , Queratinócitos/citologia , Queratinócitos/efeitos da radiação , Psoríase/patologia , Raios Ultravioleta , Biomarcadores/metabolismo , Linhagem Celular , Dinoprostona/farmacologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
2.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361071

RESUMO

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the "bath salts". Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/toxicidade , Canabidiol/farmacologia , Comportamento de Procura de Droga/efeitos dos fármacos , Pirrolidinas/toxicidade , Inibidores da Captação Adrenérgica/toxicidade , Animais , Anticonvulsivantes/farmacologia , Ansiedade/induzido quimicamente , Ansiedade/patologia , Condicionamento Clássico/efeitos dos fármacos , Masculino , Camundongos
3.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445394

RESUMO

Cytotoxic effects of cannabidiol (CBD) and tamoxifen (TAM) have been observed in several cancer types. We have recently shown that CBD primarily targets mitochondria, inducing a stable mitochondrial permeability transition pore (mPTP) and, consequently, the death of acute lymphoblastic leukemia (T-ALL) cells. Mitochondria have also been documented among cellular targets for the TAM action. In the present study we have demonstrated a synergistic cytotoxic effect of TAM and CBD against T-ALL cells. By measuring the mitochondrial membrane potential (ΔΨm), mitochondrial calcium ([Ca2+]m) and protein-ligand docking analysis we determined that TAM targets cyclophilin D (CypD) to inhibit mPTP formation. This results in a sustained [Ca2+]m overload upon the consequent CBD administration. Thus, TAM acting on CypD sensitizes T-ALL to mitocans such as CBD by altering the mitochondrial Ca2+ homeostasis.


Assuntos
Cálcio/metabolismo , Canabidiol/farmacologia , Ciclofilina D/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Tamoxifeno/farmacologia , Linhagem Celular Tumoral , Ciclofilina D/química , Sinergismo Farmacológico , Homeostase/efeitos dos fármacos , Humanos , Células Jurkat , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Conformação Proteica
4.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445404

RESUMO

Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.


Assuntos
Canabidiol/administração & dosagem , Ceramidas/sangue , Eicosanoides/sangue , Fosfolipídeos/sangue , Raios Ultravioleta/efeitos adversos , Administração Tópica , Animais , Canabidiol/farmacologia , Ceramidas/efeitos da radiação , Cromatografia de Fase Reversa , Eicosanoides/efeitos da radiação , Masculino , Fosfolipídeos/efeitos da radiação , Ratos , Ratos Nus , Espectrometria de Massas em Tandem
5.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445626

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.


Assuntos
Comportamento Animal/efeitos dos fármacos , Canabidiol/farmacologia , Fator Neurotrófico Ciliar/metabolismo , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Canais de Cátion TRPV/metabolismo , Animais , Anticonvulsivantes/farmacologia , Fator Neurotrófico Ciliar/genética , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Masculino , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/genética
6.
Biomolecules ; 11(8)2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34439801

RESUMO

The potential, multifaceted therapeutic profile of cannabidiol (CBD), a major constituent derived from the Cannabis sativa plant, covers a wide range of neurological and psychiatric disorders, ranging from anxiety to pediatric epilepsy and drug addiction. However, the molecular targets responsible for these effects have been only partially identified. In this view, the involvement of the orexin system, the key regulator in arousal and the sleep/wake cycle, and in motivation and reward processes, including drug addiction, prompted us to explore, using computational and experimental approaches, the possibility that CBD could act as a ligand of orexin receptors, orexin 1 receptor of type 1 (OX1R) and type 2 (OX2R). Ligand-binding assays showed that CBD is a selective ligand of OX1R in the low micromolar range (Ki 1.58 ± 0.2 µM) while in vitro functional assays, carried out by intracellular calcium imaging and mobilization assays, showed that CBD acts as an antagonist at this receptor. Finally, the putative binding mode of CBD has been inferred by molecular docking and molecular dynamics simulations and its selectivity toward the OX1R subtype rationalized at the molecular level. This study provides the first evidence that CBD acts as an OX1R antagonist, supporting its potential use in addictive disorders and/or body weight regulation.


Assuntos
Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Canabidiol/farmacologia , Receptores de Orexina/química , Orexinas/química , Animais , Ansiolíticos/química , Ansiolíticos/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/metabolismo , Sítios de Ligação , Células CHO , Cálcio/metabolismo , Canabidiol/química , Canabidiol/metabolismo , Cricetulus , Expressão Gênica , Humanos , Cinética , Simulação de Acoplamento Molecular , Imagem Molecular , Antagonistas dos Receptores de Orexina , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Ensaio Radioligante , Transgenes
7.
J Equine Vet Sci ; 103: 103668, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34281647

RESUMO

Cannabis sativa L. contains cannabidiol (CBD), a compound that has many anti-inflammatory properties. In this study, 99.9% CBD powder was used to determine its in vitro efficacy as an anti-inflammatory agent. Heparinized blood was collected via jugular venipuncture from senior horses. PBMCs were isolated then incubated for 24 hours with increasing dilutions of CBD dissolved in DMSO. PBMCs were stimulated the last 4 hours of incubation with PMA/IO and Brefeldin A. A Vicell counter was used to evaluate viability after incubation. PBMCs were stained intracellularly for IFNγ and TNFα then analyzed via flow cytometry. RT-PCR was used to analyze samples for gene expression. Five equine-specific intron-spanning primers/probes used are: CB1, CB2, TNFα, IFNγ, IL-10, and Beta-glucuronidase. Data was analyzed using RM One-way ANOVA (significance P < .05). Viability of PBMCs with CBD was completed to determine cytotoxicity. The dilution of CBD that did not affect cell viability was 4 µg/mL (P<0.05). CBD at 4 µg/mL significantly reduced production of IFN-γ and TNF-α (P < .05). RT-PCR results for TNFα and IFNγ at 4 µg/mL showed a reduction compared with the positive control and IL-10 showed a similar reduction at 2 µg/mL and 4 µg/mL. RT-PCR gene expression results showed significance for 10 µg/mL CBD in CB1 and CB2. CBD at 4 µg/mL reduced in vitro production of inflammatory cytokines from senior horses. This in vitro study supports further investigation of CBD to determine if it may be effective as an anti-inflammatory treatment for chronic inflammation in the horse.


Assuntos
Canabidiol , Animais , Anti-Inflamatórios/farmacologia , Canabidiol/farmacologia , Citocinas/genética , Expressão Gênica , Cavalos , Linfócitos
8.
Biomed Pharmacother ; 142: 111956, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34332377

RESUMO

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.


Assuntos
COVID-19/tratamento farmacológico , Canabidiol/farmacologia , SARS-CoV-2 , Antivirais/farmacologia , Ácido Ascórbico/farmacologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Suplementos Nutricionais , Doxiciclina/farmacologia , Reposicionamento de Medicamentos/métodos , Quimioterapia Combinada/métodos , Humanos , Ivermectina , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Vitamina D/farmacologia , Zinco/farmacologia
9.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208082

RESUMO

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.


Assuntos
Ácidos e Sais Biliares/metabolismo , Canabidiol/farmacocinética , Alimentos , Lipase/metabolismo , Disponibilidade Biológica , Canabidiol/farmacologia , Digestão , Interações Alimento-Droga , Humanos , Técnicas In Vitro , Metabolismo dos Lipídeos , Micelas
10.
J Med Chem ; 64(13): 9354-9364, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34161090

RESUMO

Cannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a partial agonist, when it binds to the orthosteric site, and a negative allosteric modulator, when it binds to the allosteric site of the cannabinoid CB2 receptor. Molecular dynamic simulations and site-directed mutagenesis studies have identified the allosteric site near the receptor entrance. This knowledge has permitted to perform structure-guided design of negative and positive allosteric modulators of the CB2 receptor with potential therapeutic utility.


Assuntos
Produtos Biológicos/farmacologia , Canabidiol/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Desenho de Fármacos , Receptor CB2 de Canabinoide/agonistas , Sítio Alostérico/efeitos dos fármacos , Produtos Biológicos/síntese química , Produtos Biológicos/química , Canabidiol/síntese química , Canabidiol/química , Agonistas de Receptores de Canabinoides/síntese química , Agonistas de Receptores de Canabinoides/química , Cannabis/química , Relação Dose-Resposta a Droga , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade
11.
Am J Sports Med ; 49(9): 2522-2527, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34097540

RESUMO

BACKGROUND: The use of cannabis is common among athletes and the US population at large. Cannabinoids are currently being evaluated as alternatives to opioid medications for chronic pain management. However, the effects of recreational and/or medical use of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on musculoskeletal injury and healing remain largely unknown. HYPOTHESIS/PURPOSE: The purpose of this study was to evaluate the biomechanical effects of CBD and THC on tendon-to-tendon healing in a rat Achilles tendon repair model. The hypothesis was that rats administered CBD would demonstrate decreased tensile load to failure of surgically repaired Achilles tendons compared with the THC and control groups. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 33 Sprague Dawley rats underwent Achilles tendon surgical transection and repair and were randomized to receive subcutaneous injection of THC, CBD, or vehicle once daily starting on the day of surgery and for 5 total days. After sacrifice, biomechanical tensile load-displacement testing was performed to determine Achilles tendon load to failure and stiffness. Data were analyzed by 1-way analysis of variance. RESULTS: The THC group demonstrated the highest median load to failure, 18.7 N (95% CI, 15.3-19.2 N); the CBD group had the second highest at 16.9 N (95% CI, 15.1-19.8 N), and the control group had the lowest at 14.4 N (95% CI, 12.1-18.3 N). Stiffness was highest in the THC group at 4.1 N/mm (95% CI, 2.7-5.1 N/mm) compared with 3.6 N/mm (95% CI, 2.9-4.1 N/mm) for the CBD group and 3.6 N/mm (95% CI, 2.8-4.3 N/mm) for the control group. No statistically significant differences for strength and stiffness were observed between the groups. CONCLUSION: In this pilot study using an animal tendon-to-tendon repair model, neither THC nor CBD resulted in altered biomechanical characteristics compared to control. CLINICAL RELEVANCE: Cannabinoids do not appear to adversely affect Achilles tendon healing.


Assuntos
Tendão do Calcâneo , Canabidiol , Cannabis , Tendão do Calcâneo/cirurgia , Animais , Canabidiol/farmacologia , Dronabinol/farmacologia , Projetos Piloto , Ratos , Ratos Sprague-Dawley
12.
Molecules ; 26(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073361

RESUMO

CBD is a promising candidate for treatment of many diseases and plays a major role in the growing trend to produce high-end drugs from natural, renewable resources. In the present work, we demonstrate a way to incorporate the anti-inflammatory drug CBD into smart microgel particles. The copolymer microgels that we chose as carrier systems exhibit a volume phase transition temperature of 39 ∘C, which is just above normal body temperature and makes them ideal candidates for hyperthermia treatment. While a simple loading route of CBD was not successful due to the enormous hydrophobicity of CBD, an alternative route was developed by immersing the microgels in ethanol. Despite the expected loss of thermoresponsive behaviour of the microgel matrix due to the solvent exchange, a temperature-dependent release of CBD was detected by the material, creating an interesting question of interactions between CBD and the microgel particles in ethanol. Furthermore, the method developed for loading of the microgel particles with CBD in ethanol was further improved by a subsequent transfer of the loaded particles into water, which proves to be an even more promising approach due to the successful temperature-dependent release of the drug above the collapse temperature of the microgels.


Assuntos
Anti-Inflamatórios/farmacologia , Canabidiol/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microgéis , Acrilamidas/química , Anti-Inflamatórios/análise , Canabidiol/análise , Etanol , Géis , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Transição de Fase , Fótons , Polímeros/química , Espalhamento de Radiação , Solventes , Espectrofotometria Ultravioleta , Tensoativos , Temperatura
13.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062987

RESUMO

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.


Assuntos
Canabidiol/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Terapia de Alvo Molecular , Animais , Canabidiol/química , Canabidiol/farmacologia , Humanos , Canais Iônicos/metabolismo , Modelos Moleculares
14.
Biomolecules ; 11(5)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065479

RESUMO

The success of cannabinoids with chronic neuropathic pain and anxiety has been demonstrated in a multitude of studies. With the high availability of a non-intoxicating compound, cannabidiol (CBD), an over-the-counter medication, has generated heightened interest in its use in the field of oncology. This review focuses on the widespread therapeutic potential of CBD with regard to enhanced wound healing, lowered toxicity profiles of chemotherapeutics, and augmented antitumorigenic effects. The current literature is sparse with regard to determining the clinically relevant concentrations of CBD given the biphasic nature of the compound's response. Therefore, there is an imminent need for further dose-finding studies in order to determine the optimal dose of CBD for both intermittent and regular users. We address the potential influence of regular or occasional CBD usage on therapeutic outcomes in ovarian cancer patients. Additionally, as the development of chemoresistance in ovarian cancer results in treatment failure, the potential for CBD to augment the efficacy of conventional chemotherapeutic and epigenetic drugs is a topic of significant importance. Our review is focused on the widespread therapeutic potential of CBD and whether or not a synergistic role exists in combination with epigenetic and classic chemotherapy medications.


Assuntos
Antineoplásicos/uso terapêutico , Canabidiol/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos/farmacologia , Canabidiol/farmacologia , Sinergismo Farmacológico , Epigênese Genética/efeitos dos fármacos , Feminino , Humanos , Medicamentos sem Prescrição , Neoplasias Ovarianas/genética , Resultado do Tratamento
15.
Phytother Res ; 35(9): 5269-5281, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173287

RESUMO

The aim of study was to evaluate and compare the phytochemical profile, the antioxidant and antimicrobial properties of two standardized extracts from non-psychotropic (Δ9 -tetrahydrocannabinol ≤0.2%) Cannabis sativa L. var. fibrante rich in cannabidiol (CBD). The two extracts, namely Cannabis Fibrante Hexane Extract 1 (CFHE1) and Cannabis Fibrante Hexane Extract 2 (CFHE2), were obtained by extraction with acidified hexane from dried flowering tops as such and after hydrodistillation of the essential oil, respectively. Gas chromatographic analysis showed that cannabinoids remained the predominant class of compounds in both extracts (82.56% and 86.38%, respectively), whereas a marked depletion of the terpenes occurred. Moreover, liquid chromatographic analysis highlighted a high titer of cannabidiol acid (CBDA) and CBD in CFHE1 and CFHE2, respectively. Both extracts showed a strong and concentration-dependent antioxidant activity and a potent antimicrobial activity against both Staphylococcus aureus ATCC 6538 (MIC and MBC of 4.88 µg/ml for CFHE1, and 4.88 and 19.53 µg/ml, respectively, for CFHE2) and methicillin resistant clinical strains (MIC values between 1.22 and 9.77 µg/ml and MBC values between 4.88 and 78.13 µg/ml). Considering this, the obtained results suggest that standardized extracts of C. sativa var. fibrante could find promising applications as novel antimicrobial agents.


Assuntos
Canabidiol , Cannabis , Extratos Vegetais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Canabidiol/farmacologia , Dronabinol , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
16.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073710

RESUMO

Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ. Spontaneous network activity measurements were obtained using a multielectrode array at baseline and following administration of CBD or ILO alone, or combined. At baseline, MAM male neurons displayed increased bursting activity whereas MAM female neurons exhibited no difference in bursting activity compared to sex-matched controls. CBD administered alone showed a rapid but transient increase in neuronal activity in the MAM networks, an effect more pronounced in females. Furthermore, ILO had an additive effect on CBD-induced elevations in activity in the MAM male neurons. In the MAM female neurons, CBD or ILO administration resulted in time-dependent elevations in neuronal activity, but the short-term CBD-induced increases in activity were lost when CBD and ILO were combined. Our findings indicate that CBD induces rapid increases in cortical neuronal activity, with sex-specific drug interactions upon ILO coadministration. This suggests that sex should be a consideration when implementing adjunct therapy for treatment of SZ.


Assuntos
Canabidiol/farmacologia , Isoxazóis/farmacologia , Neurônios/efeitos dos fármacos , Piperidinas/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Animais Recém-Nascidos , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Canabidiol/uso terapêutico , Técnicas de Cultura de Células , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Feminino , Isoxazóis/uso terapêutico , Masculino , Neurônios/fisiologia , Piperidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Esquizofrenia/fisiopatologia , Caracteres Sexuais
17.
Nutrients ; 13(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064937

RESUMO

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas-liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.


Assuntos
Canabidiol/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-6/farmacologia , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Cannabis , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados , Inflamação , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos , Lipídeos , Masculino , Obesidade/induzido quimicamente , Ratos , Ratos Wistar
18.
J Transl Med ; 19(1): 220, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030718

RESUMO

BACKGROUND: The phytocannabinoid cannabidiol (CBD) exhibits anxiolytic activity and has been promoted as a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense. METHODS: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged 1 h later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements. RESULTS: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex. CONCLUSION: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress.


Assuntos
Canabidiol , Animais , Encéfalo , Canabidiol/farmacologia , Medo , Imageamento por Ressonância Magnética , Camundongos , Vigília
19.
Phytomedicine ; 88: 153533, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33812759

RESUMO

INTRODUCTION: The increased incidence of Glioblastoma Multiforme, the most aggressive and most common primary brain tumour, is evident worldwide. Survival rates are reaching only 15 months due to its high recurrence and resistance to current combination therapies including oncotomy, radiotherapy and chemotherapy. Light has been shed in the recent years on the anticancer properties of cannabinoids from Cannabis sativa. OBJECTIVE: To determine whether cannabinoids alone or in combination with radiotherapy and/or chemotherapy inhibit tumour progression, induce cancer cell death, inhibit metastasis and invasiveness and the mechanisms that underlie these actions. METHOD: PubMed and Web of Science were used for a systemic search to find studies on the anticancer effects of natural cannabinoids on glioma cancer cells in vitro and/or in vivo. RESULTS: A total of 302 papers were identified, of which 14 studies were found to fit the inclusion criteria. 5 studies were conducted in vitro, 2 in vivo and 7 were both in vivo and in vitro. 3 studies examined the efficacy of CBD, THC and TMZ, 1 study examined CBD and radiation, 2 studies examined efficacy of THC only and 3 studies examined the efficacy of CBD only. 1 study examined the efficacy of CBD, THC and radiotherapy, 2 studies examined the combination of CBD and THC and 2 more studies examined the efficacy of CBD and TMZ. CONCLUSION: The evidence in this systematic review leads to the conclusion that cannabinoids possess anticancer potencies against glioma cells, however this effect varies with the combinations and dosages used. Studies so far were conducted on cells in culture and on mice as well as a small number of studies that were conducted on humans. Hence in order to have more accurate results, higher quality studies mainly including human clinical trials with larger sample sizes are necessitated urgently for GBM treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Canabinoides/farmacologia , Glioblastoma/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Canabidiol/farmacologia , Canabinoides/administração & dosagem , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Camundongos
20.
Br J Pharmacol ; 178(15): 3067-3078, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33822373

RESUMO

BACKGROUND AND PURPOSE: Cannabidiol (CBD) is a non-euphorigenic component of Cannabis sativa that prevents the development of paclitaxel-induced mechanical sensitivity in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). We recently reported that the CBD structural analogue KLS-13019 shows efficacy in an in vitro model of CIPN. The present study was to characterize the behavioural effects of KLS-13019 compared to CBD and morphine in mouse models of CIPN, nociceptive pain and reinforcement. EXPERIMENTAL APPROACH: Prevention or reversal of paclitaxel-induced mechanical sensitivity were assessed following intraperitoneal or oral administration of CBD, KLS-13019 or morphine. Antinociceptive activity using acetic acid-induced stretching and hot plate assay, anti-reinforcing effects on palatable food or morphine self-administration and binding to human opioid receptors were also determined. KEY RESULTS: Like CBD, KLS-13019 prevented the development of mechanical sensitivity associated with paclitaxel administration. In contrast to CBD, KLS-13019 was also effective at reversing established mechanical sensitivity. KLS-13019 significantly attenuated acetic acid-induced stretching and produced modest effects in the hot plate assay. KLS-13019 was devoid of activity at µ-, δ- or κ-opioid receptors. Lastly, KLS-13019, but not CBD, attenuated the reinforcing effects of palatable food or morphine. CONCLUSIONS AND IMPLICATIONS: KLS-13019 like CBD, prevented the development of CIPN, while KLS-13019 uniquely attenuated established CIPN. Because KLS-13019 binds to fewer biological targets, this will help to identifying molecular mechanisms shared by these two compounds and those unique to KLS-13019. Lastly, KLS-13019 may possess the ability to attenuate reinforced behaviour, an effect not observed in the present study with CBD.


Assuntos
Canabidiol , Dor Nociceptiva , Animais , Canabidiol/farmacologia , Modelos Animais de Doenças , Camundongos , Morfina , Reforço Psicológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...