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1.
Eur J Cell Biol ; 101(1): 151185, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915361

RESUMO

The PINK1/Parkin pathway plays an important role in maintaining a healthy pool of mitochondria. Activation of this pathway can lead to apoptosis, mitophagy, or mitochondrial-derived vesicle formation, depending on the nature of mitochondrial damage. The signaling by which PINK/Parkin activation leads to these different mitochondrial outcomes remains understudied. Here we present evidence that cannabidiol (CBD) activates the PINK1-Parkin pathway in a unique manner. CBD stimulates PINK1-dependent Parkin mitochondrial recruitment similarly to other well-studied Parkin activators but with a distinctive shift in the temporal dynamics and mitochondrial fates. The mitochondrial permeability transition pore inhibitor cyclosporine A exclusively diminished the CBD-induced PINK1/Parkin activation and its associated mitochondrial effects. Unexpectedly, CBD treatment also induced elevated production of mitochondrial-derived vesicles (MDV), a potential quality control mechanism that may help repair partial damaged mitochondria. Our results suggest that CBD may engage the PINK1-Parkin pathway to produce MDV and repair mitochondrial lesions via mitochondrial permeability transition pore opening. This work uncovered a novel link between CBD and PINK1/Parkin-dependent MDV production in mitochondrial health regulation.


Assuntos
Canabidiol , Mitofagia , Mitocôndrias , Proteínas Quinases , Ubiquitina-Proteína Ligases
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 268: 120682, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34906842

RESUMO

The isomers cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) can both be extracted from cannabis. We use density functional theory to study the Raman activity spectra, frontier molecular orbitals, and molecular electrostatic potentials of CBD, THC, and their respective gold complexes. A "selectivity enhancement" phenomenon for the spectral peaks at frequencies of 1144 cm-1 and 1553 cm-1 in the Raman spectrum of the CBD-Aun complex, and at frequencies of 865 cm-1, 1335 cm-1, and 1553 cm-1 in the Raman spectrum of the THC-Aun complex, was observed and explained. The frontier molecular orbital energy gaps of CBD and THC are 5.4085 eV and 5.4461 eV, respectively, indicating that CBD is more likely to react than THC. The CBD/THC-Au complexes had the strongest chemical activities and greater charge transfer effects with an Au3 cluster. The most electronegative sites of CBD and THC were found from molecular electrostatic potential (MEP) mapping. It is assumed that these sites are the adsorption sites of the CBD/THC molecules and gold surface. The MEP of the CBD/THC complexes also demonstrates the charge transfer effect between CBD/THC and Au. Both the "selectivity" phenomenon in the Raman activity spectra of the complex and the above assumption are explained by a surface selection rule. The conformation of the CBD/THC molecules on the gold surface are determined, showing that CBD is adsorbed vertically through the resorcinol structure while THC is adsorbed vertically through the tetrahydropyran and benzene ring.


Assuntos
Canabidiol , Nanopartículas Metálicas , Teoria da Densidade Funcional , Dronabinol , Ouro , Análise Espectral Raman
3.
Talanta ; 237: 122905, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736642

RESUMO

Herein we report on the early detection of cannabinoids in urine samples according to their affinity profiles in competitive assays with labelled ghrelin (GHR). We have demonstrated for the first time that cannabidiol (CBD) and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) act as extracellular ligands for the growth hormone secretagogue receptor (GHS-R1a), strongly promoting the binding of ghrelin (GHR), the endogenous ligand of GHS-R1a. The affinity profiles of CBD and carboxy-THC are significantly different from the profiles of synthetic GHR mimetics such as CJC-1295 or [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-Substance P peptides, which are the most common interferents; the cannabinoids promoted the GHR/GHS-R1a interaction, while the ghrelin mimetics acted rather as competitive inhibitors. The analysis of 1:4 diluted urine samples proved that the proposed method displays good linearity and sensitivity in the range of 5-30 ng/mL for both CBD and carboxy-THC, whereas GHR mimetics display no interference at concentrations up to 100 ng/mL. The results were validated by comparison with the gas chromatography tandem mass spectrometry reference method. CBD may exert the same promoting effect on the interaction of GHS-R1a with other GHR mimetics listed as performance-enhancing substances.


Assuntos
Canabidiol , Canabinoides , Canabidiol/análise , Canabinoides/análise , Dronabinol/análise , Cromatografia Gasosa-Espectrometria de Massas , Receptores de Grelina
4.
Clin Dermatol ; 39(6): 1014-1017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34920818

RESUMO

Cannabinoids represent a diverse group of pharmacologic compounds that have recently grown in popularity for its use in medicine. One of the cannabinoids of the Cannabis plant is cannabidiol (CBD), which is a compound known to regulate physiologic processes. Despite limited high-quality clinical evidence, topical CBD-containing products are frequently marketed to consumers as possessing antiinflammatory, hydrating, moisturizing, and wrinkle-reducing properties. Here, we explored the trends in consumer interest for topical CBD products by querying a popular online search engine database from 2015 to 2019 to offer valuable insights.


Assuntos
Canabidiol , Humanos
5.
J Med Internet Res ; 23(12): e27307, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34932014

RESUMO

BACKGROUND: In the absence of official clinical trial information, data from social networks can be used by public health and medical researchers to assess public claims about loosely regulated substances such as cannabidiol (CBD). For example, this can be achieved by comparing the medical conditions targeted by those selling CBD against the medical conditions patients commonly treat with CBD. OBJECTIVE: The objective of this study was to provide a framework for public health and medical researchers to use for identifying and analyzing the consumption and marketing of unregulated substances. Specifically, we examined CBD, which is a substance that is often presented to the public as medication despite complete evidence of efficacy and safety. METHODS: We collected 567,850 tweets by searching Twitter with the Tweepy Python package using the terms "CBD" and "cannabidiol." We trained two binary text classifiers to create two corpora of 167,755 personal use and 143,322 commercial/sales tweets. Using medical, standard, and slang dictionaries, we identified and compared the most frequently occurring medical conditions, symptoms, side effects, body parts, and other substances referenced in both corpora. In addition, to assess popular claims about the efficacy of CBD as a medical treatment circulating on Twitter, we performed sentiment analysis via the VADER (Valence Aware Dictionary for Sentiment Reasoning) model on the personal CBD tweets. RESULTS: We found references to medically relevant terms that were unique to either personal or commercial CBD tweet classes, as well as medically relevant terms that were common to both classes. When we calculated the average sentiment scores for both personal and commercial CBD tweets referencing at least one of 17 medical conditions/symptoms terms, an overall positive sentiment was observed in both personal and commercial CBD tweets. We observed instances of negative sentiment conveyed in personal CBD tweets referencing autism, whereas CBD was also marketed multiple times as a treatment for autism within commercial tweets. CONCLUSIONS: Our proposed framework provides a tool for public health and medical researchers to analyze the consumption and marketing of unregulated substances on social networks. Our analysis showed that most users of CBD are satisfied with it in regard to the condition that it is being advertised for, with the exception of autism.


Assuntos
Canabidiol , Mídias Sociais , Atitude , Humanos , Saúde Pública
6.
Am J Vet Res ; 83(1): 86-94, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34727050

RESUMO

OBJECTIVE: To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs. ANIMALS: 9 healthy, purpose bred Beagles. PROCEDURES: A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study. RESULTS: Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14. CONCLUSIONS AND CLINICAL RELEVANCE: No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.


Assuntos
Canabidiol , Preparações Farmacêuticas , Animais , Cães , Interações Medicamentosas , Fenobarbital , Estudos Prospectivos
7.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641624

RESUMO

(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal-if not scientific or clinical-evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.


Assuntos
Canabidiol/farmacologia , Células-Tronco Neurais/citologia , Neuroglia/citologia , Neurônios/citologia , Animais , Canabidiol/química , Células Cultivadas , Humanos , Estrutura Molecular , Células-Tronco Neurais/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Cultura Primária de Células
8.
J Vet Pharmacol Ther ; 44(6): 870-882, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34605042

RESUMO

Medical use of Cannabis (or hemp) began thousands of years ago. In the 20th century, mechanisms of action were demonstrated with the discovery of its active substances, the phytocannabinoids, and its pharmacological targets, the endocannabinoid system. This system is composed of receptors, endogenous substances, and enzymes, and it participates in the modulation of physiological mechanisms in several species, including dogs. Studies indicate that changes in this system may contribute to the genesis of some diseases. Therefore, the use of substances that act on its components may help in the treatment of these diseases. The main phytocannabinoids described are Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD). In humans, the benefits of using CBD in several diseases have been demonstrated. The popularization of this type of treatment has also reached veterinary medicine, which on one hand was related to an increase in adverse event records, but on the other also allowed reports of anecdotal evidences of its effectiveness and safety in animals. Clinical studies published so far indicate that the use of CBD in dogs can be safe at given doses and can contribute to osteoarthritis and idiopathic epilepsy treatments. Clinical and pre-clinical studies and case reports were reviewed in this report to identify the main characteristics of hemp-based therapies in dogs, including its pharmacokinetics, pharmacodynamics, safety, and efficacy in the treatment of diseases.


Assuntos
Canabidiol , Cannabis , Animais , Proteínas de Transporte , Cães , Dronabinol
9.
Int J Pharm ; 609: 121159, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34624443

RESUMO

Herein, medium-chain triglycerides (MCT), glyceryl monolinoleate (GML), and a self-emulsifying drug delivery system (SEDDS) for cannabidiol (CBD) delivery were compared using in vitro and in vivo (mouse and human) studies. In vitro digestion tests showed that SEDDS yielded the highest CBD recovery in the aqueous phase (86 ± 2%), followed by GML (13 ± 2%) and MCT (5.6% ± 0.8%). In vivo tests (mouse) revealed that SEDDS promoted the highest CBD exposure, exhibiting an area under the plasma concentration-time curve (AUC0-6h) 1.48 times greater than GML and 3.97 times greater than that of the MCT formulation. A single-dose, open-label, crossover study performed in 11 volunteers showed that SEDDS increased CBD AUC0-12h by 1.12 and 1.48 times in relation to GML and MCT, respectively. The in vitro-in vivo correlation was r2 0.75 for mice and r2 0.66 for humans. The AUC correlation between mice and humans was 0.98. Collectively, these results indicate that the lipid profile substantially influences CBD delivery and highlights the potential of the SEDDS and GML formulations as candidate solutions for increasing CBD AUC and bioavailability.


Assuntos
Canabidiol , Lipídeos , Administração Oral , Animais , Disponibilidade Biológica , Estudos Cross-Over , Digestão , Sistemas de Liberação de Medicamentos , Emulsões , Humanos , Camundongos , Solubilidade
10.
Seizure ; 92: 238-243, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34624613

RESUMO

OBJECTIVE: Here we present a series of patients with WS that were refractory to antiseizure medications and the ketogenic diet and who were treated with cannabidiol-enriched cannabis oil (CBD) as add-on therapy analyzing efficacy, safety, and tolerability. MATERIAL AND METHODS: Medical records of eight patients with WS treated with CBD at a ratio of cannabidiol:Δ-9-tetrahydrocannabinol (CBD:THC) of 25:1 seen between May 2020 and March 2021 were retrospectively analyzed. In all patients CBD was started as add-on therapy. RESULTS: Eight patients (six female and two male) who received CBD for treatment-resistant WS were evaluated. Ages ranged from 16 to 22 months. The etiology was unknown in five and structural in three. Initial CBD dose was 2 mg/kg/day which was uptitrated to a median dose of 12 mg/kg/day (range, 2-25). Prior to CBD initiation, patients had a mean of 63 seizures per day (range, 31-79). After a follow-up of between 6 and 13 months, a 75-99% decrease in seizure frequency was observed in two patients, a 50-74% decrease in two, a less than 50% decrease in three, and no changes in seizure frequency were seen in the remaining patient. The index of EEG abnormalities improved between 20 and 80% in seven patients concurrently with the reduction in seizures. Adverse effects were mild and transient. Somnolence was observed in one patient, nausea and vomiting in one, and behavior disturbances and irritability in another patient. CONCLUSION: This study evaluating the use of cannabidiol-enriched cannabis oil in children with WS showed that four (50%) of eight had a more than 50% seizure reduction with good tolerability.


Assuntos
Canabidiol , Epilepsia Resistente a Medicamentos , Epilepsia , Maconha Medicinal , Espasmos Infantis , Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Criança , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Maconha Medicinal/uso terapêutico , Estudos Retrospectivos , Espasmos Infantis/tratamento farmacológico
11.
BMJ Case Rep ; 14(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649854

RESUMO

Conventional lung cancer treatments include surgery, chemotherapy and radiotherapy; however, these treatments are often poorly tolerated by patients. Cannabinoids have been studied for use as a primary cancer treatment. Cannabinoids, which are chemically similar to our own body's endocannabinoids, can interact with signalling pathways to control the fate of cells, including cancer cells. We present a patient who declined conventional lung cancer treatment. Without the knowledge of her clinicians, she chose to self-administer 'cannabidiol (CBD) oil' orally 2-3 times daily. Serial imaging shows that her cancer reduced in size progressively from 41 mm to 10 mm over a period of 2.5 years. Previous studies have failed to agree on the usefulness of cannabinoids as a cancer treatment. This case appears to demonstrate a possible benefit of 'CBD oil' intake that may have resulted in the observed tumour regression. The use of cannabinoids as a potential cancer treatment justifies further research.


Assuntos
Canabidiol , Canabinoides , Neoplasias Pulmonares , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico
12.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641522

RESUMO

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Canabidiol/farmacologia , Maleato de Dizocilpina/toxicidade , Memória/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Locomoção/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos , Esquizofrenia/etiologia
13.
J Vet Pharmacol Ther ; 44(6): 967-974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34658021

RESUMO

Cannabidiol (CBD) has gained widespread popularity as a treatment for osteoarthritis (OA) in pets; however, there is minimal scientific evidence regarding safe and effective dosing. This study determined plasma and tissue pharmacokinetics after oral CBD oil suspension administration in Hartley guinea pigs (Cavia porcellus), which spontaneously develop OA at 3 months of age. Ten, 5-month-old, male guinea pigs were randomly assigned to receive 25 (n = 5) or 50 mg/kg (n = 5) CBD oil once orally. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 h timepoints. Open-field enclosure monitoring revealed no adverse effects. After euthanasia, stifle cartilage and infrapatellar fat pads were collected to quantitate CBD. CBD concentrations were determined using a validated liquid chromatography-mass spectrometry method, and pharmacokinetic parameters were calculated using noncompartmental analysis. The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively. CBD was detected in joint tissues of all animals. Further studies, including work in female guinea pigs, are needed to determine the efficacy of CBD for OA.


Assuntos
Canabidiol , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida/veterinária , Feminino , Cobaias , Masculino , Espectrometria de Massas/veterinária
14.
J Med Internet Res ; 23(10): e25730, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704957

RESUMO

BACKGROUND: Insomnia is a prevalent condition that presents itself at both the symptom and diagnostic levels. Although insomnia is one of the main reasons individuals seek medicinal cannabis, little is known about the profile of cannabinoid use or the perceived benefit of the use of cannabinoids in daily life. OBJECTIVE: We conducted a retrospective study of medicinal cannabis users to investigate the use profile and perceived efficacy of cannabinoids for the management of insomnia. METHODS: Data were collected using the Strainprint app, which allows medicinal cannabis users to log conditions and symptoms, track cannabis use, and monitor symptom severity pre- and postcannabis use. Our analyses examined 991 medicinal cannabis users with insomnia across 24,189 tracked cannabis use sessions. Sessions were analyzed, and both descriptive statistics and linear mixed-effects modeling were completed to examine use patterns and perceived efficacy. RESULTS: Overall, cannabinoids were perceived to be efficacious across all genders and ages, and no significant differences were found among product forms, ingestion methods, or gender groups. Although all strain categories were perceived as efficacious, predominant indica strains were found to reduce insomnia symptomology more than cannabidiol (CBD) strains (estimated mean difference 0.59, SE 0.11; 95% CI 0.36-0.81; adjusted P<.001) and predominant sativa strains (estimated mean difference 0.74, SE 0.16; 95% CI 0.43-1.06; adjusted P<.001). Indica hybrid strains also presented a greater reduction in insomnia symptomology than CBD strains (mean difference 0.52, SE 0.12; 95% CI 0.29-0.74; adjusted P<.001) and predominant sativa strains (mean difference 0.67, SE 0.16; 95% CI 0.34-1.00; adjusted P=.002). CONCLUSIONS: Medicinal cannabis users perceive a significant improvement in insomnia with cannabinoid use, and this study suggests a possible advantage with the use of predominant indica strains compared with predominant sativa strains and exclusively CBD in this population. This study emphasizes the need for randomized placebo-controlled trials assessing the efficacy and safety profile of cannabinoids for the treatment of insomnia.


Assuntos
Canabidiol , Canabinoides , Cannabis , Distúrbios do Início e da Manutenção do Sono , Canabinoides/uso terapêutico , Humanos , Estudos Retrospectivos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico
15.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502487

RESUMO

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , COVID-19/tratamento farmacológico , Canabidiol/uso terapêutico , Interações Medicamentosas , Nutrientes/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , COVID-19/virologia , Canabidiol/química , Canabidiol/farmacocinética , Carbamazepina/química , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Clobazam/química , Clobazam/farmacocinética , Clobazam/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Humanos , SARS-CoV-2/isolamento & purificação
16.
Aust J Gen Pract ; 50(10): 724-732, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34590094

RESUMO

BACKGROUND: Chronic pain is a major health issue, adversely affecting millions of Australians and costing billions of dollars annually. Current pharmaceutical treatments may be limiting, and in some cases ineffective, while carrying substantial liabilities. Medicinal cannabis is an increasingly popular, albeit controversial, alternative. OBJECTIVE: The aim of this article is to briefly review the scientific evidence related to medicinal cannabis for the treatment of chronic pain and update physicians on relevant issues and optimal prescribing practices. DISCUSSION: To date, >130,000 medicinal cannabis approvals have been issued in Australia, mostly by general practitioners, with approximately 65% of these to treat chronic non-cancer pain. Available products deliver Δ9-tetrahydrocannabinol (THC) and/or cannabidiol (CBD). Despite robust supportive data from animal models, current clinical trial evidence for THC and CBD efficacy in chronic pain is incomplete. In their prescribing decisions, doctors must balance patient demand and curiosity with caution regarding potential risks and limited efficacy.


Assuntos
Canabidiol , Dor Crônica , Maconha Medicinal , Analgésicos Opioides , Animais , Austrália , Canabidiol/uso terapêutico , Dor Crônica/tratamento farmacológico , Humanos , Maconha Medicinal/efeitos adversos
17.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575932

RESUMO

(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the Cannabis Sativa and Indica plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of Cannabis extracts (Bedrocan, FM2) or selected cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ9-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.


Assuntos
Canabidiol/farmacologia , Dronabinol/farmacologia , Glucose/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Animais , Cannabis/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
18.
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
19.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576212

RESUMO

Currently, no treatment can completely cure pulmonary hypertension (PH), which can lead to right ventricular failure and, consequently, death. Therefore, searching for new therapies remains important. Increased resistance in pulmonary circulation is mainly caused by the excessive contraction and proliferation of small pulmonary arteries. Cannabinoids, a group of lipophilic compounds that all interact with cannabinoid receptors, exert a pulmonary vasodilatory effect through several different mechanisms, including mechanisms that depend on vascular endothelium and/or receptor-based mechanisms, and may also have anti-proliferative and anti-inflammatory properties. The vasodilatory effect is important in regulating pulmonary resistance, which can improve patients' quality of life. Moreover, experimental studies on the effects of cannabidiol (plant-derived, non-psychoactive cannabinoid) in animal PH models have shown that cannabidiol reduces right ventricular systolic pressure and excessive remodelling and decreases pulmonary vascular hypertrophy and pulmonary vascular resistance. Due to the potentially beneficial effects of cannabinoids on pulmonary circulation and PH, in this work, we review whether cannabinoids can be used as an adjunctive therapy for PH. However, clinical trials are still needed to recommend the use of cannabinoids in the treatment of PH.


Assuntos
Canabinoides/metabolismo , Hipertensão Pulmonar/terapia , Animais , Anti-Inflamatórios/farmacologia , Canabidiol/farmacologia , Proliferação de Células , Modelos Animais de Doenças , Endocanabinoides/metabolismo , Ventrículos do Coração , Humanos , Técnicas In Vitro , Ligantes , Pulmão/metabolismo , Óxido Nítrico , Circulação Pulmonar , Receptores de Canabinoides/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sístole , Vasoconstrição , Vasodilatação , Disfunção Ventricular Direita
20.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34576262

RESUMO

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN-38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN-38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II ß and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN-38 (CSN-38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN-38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of CBD and its synergistic combination with SN-38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.


Assuntos
Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Canabidiol/química , Proteômica/métodos , Adenocarcinoma/metabolismo , Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Canabidiol/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Dactinomicina/análogos & derivados , Dactinomicina/farmacologia , Docetaxel/química , Docetaxel/metabolismo , Doxorrubicina/química , Doxorrubicina/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Irinotecano/química , Irinotecano/metabolismo , Células MCF-7 , Paclitaxel/química , Paclitaxel/metabolismo , Proteoma , Vinorelbina/química , Vinorelbina/metabolismo
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