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1.
Exp Dermatol ; 33(7): e15144, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39039940

RESUMO

The endocannabinoid system is composed by a complex and ubiquitous network of endogenous lipid ligands, enzymes for their synthesis and degradation, and receptors, which can also be stimulated by exogenous compounds, such as those derived from the Cannabis sativa. Cannabis and its bioactive compounds, including cannabinoids and non-cannabinoids, have been extensively studied in different conditions. Recent data have shown that the endocannabinoid system is responsible for maintaining the homeostasis of various skin functions such as proliferation, differentiation and release of inflammatory mediators. Because of their role in regulating these key processes, cannabinoids have been studied for the treatment of skin cancers and melanoma; their anti-tumour effects regulate skin cancer progression and are mainly related to the inhibition of tumour growth, proliferation, invasion and angiogenesis, through apoptosis and autophagy induction. This review aims at summarising the current field of research on the potential uses of cannabinoids in the melanoma field.


Assuntos
Canabinoides , Melanoma , Neoplasias Cutâneas , Humanos , Canabinoides/uso terapêutico , Canabinoides/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Endocanabinoides/metabolismo , Endocanabinoides/uso terapêutico , Animais , Apoptose/efeitos dos fármacos
2.
Sci Rep ; 14(1): 16242, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004628

RESUMO

Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.


Assuntos
Canabinoides , Neuralgia , Animais , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Camundongos , Canabinoides/farmacologia , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Masculino , Humanos , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo
3.
CNS Drugs ; 38(8): 597-612, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38951463

RESUMO

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.


Assuntos
Canabinoides , Dor , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Canabinoides/efeitos adversos , Canabinoides/síntese química , Dor/tratamento farmacológico , Animais , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Medicamentos Sintéticos/farmacologia , Medicamentos Sintéticos/uso terapêutico
4.
Toxicol In Vitro ; 99: 105888, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38950639

RESUMO

Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function. We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis. Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 µM) or the pro-inflammatory cytokines TNFα and IL-1ß (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 µM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 µM). Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation. These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.


Assuntos
Canabidiol , Canabinoides , Mucosa Intestinal , Irinotecano , Espécies Reativas de Oxigênio , Humanos , Células CACO-2 , Canabidiol/farmacologia , Canabinoides/farmacologia , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Função da Barreira Intestinal , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Irinotecano/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
J Breath Res ; 18(4)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39008974

RESUMO

Cannabinoids can be detected in breath after cannabis use, but different breath matrices need to be explored as studies to date with filter-based devices that collect breath aerosols have not demonstrated that breath-based measurements can reliably identify recent cannabis use. Exhaled breath condensate (EBC) is an unexplored aqueous breath matrix that contains condensed volatile compounds and water vapor in addition to aerosols. EBC was collected from participants both before and at two time points (0.7 ± 0.2 h and 1.7 ± 0.3 h) after observed cannabis use. Eleven different cannabinoids were monitored with liquid chromatography tandem mass spectrometry. Five different cannabinoids, including Δ9-tetrahydrocannabinol (THC), were detected in EBC collected from cannabis users. THC was detected in some EBC samples before cannabis use, despite the requested abstinence period. THC was detected in all EBC samples collected at 0.7 h post use and decreased for all participants at 1.7 h. Non-THC cannabinoids were only detected after cannabis use. THC concentrations in EBC samples collected at 0.7 h showed no trend with sample metrics like mass or number of breaths. EBC sampling devices deserve further investigation with respect to modes of cannabis use (e.g, edibles), post use time points, and optimization of cannabinoid recovery.


Assuntos
Testes Respiratórios , Canabinoides , Expiração , Humanos , Testes Respiratórios/métodos , Canabinoides/análise , Masculino , Adulto , Feminino , Espectrometria de Massas em Tandem/métodos , Adulto Jovem , Cromatografia Líquida/métodos , Detecção do Abuso de Substâncias/métodos , Fumar Maconha/efeitos adversos , Dronabinol/análise , Cannabis/química
6.
Fitoterapia ; 177: 106128, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025316

RESUMO

The long-term stability in real and accelerated time for galenic oils based on full-spectrum cannabis has been studied, using sesame oil as a dilutant. Sesame oil is one of the most used vehicles in the cannabis pharmaceutical industry due to the costs and increased oral bioavailability of cannabinoids. The real-time assays conducted at 25 °C over twelve months demonstrated high stability and showed no significant changes in the composition of cannabinoids, total polyphenols, flavonoids, or antioxidant capacity. In these studies, it was observed that there was no development of microorganisms compromising the stability of the oils over a year. The three oil varieties exhibited a high bactericidal capacity against E. coli, S. aureus, and P. larvae.


Assuntos
Antibacterianos , Antioxidantes , Cannabis , Escherichia coli , Óleos de Plantas , Cannabis/química , Antibacterianos/farmacologia , Antibacterianos/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Estabilidade de Medicamentos , Óleo de Gergelim/química , Óleo de Gergelim/farmacologia , Canabinoides/farmacologia , Canabinoides/química , Larva/efeitos dos fármacos , Polifenóis/farmacologia , Polifenóis/química , Flavonoides/farmacologia , Flavonoides/química
7.
Cells ; 13(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38920643

RESUMO

Neurodegenerative disorders are affecting millions of people worldwide, impacting the healthcare system of our society. Among them, Alzheimer's disease (AD) is the most common form of dementia, characterized by severe cognitive impairments. Neuropathological hallmarks of AD are ß-amyloid (Aß) plaques and neurofibrillary tangles, as well as endoplasmic reticulum and mitochondria dysfunctions, which finally lead to apoptosis and neuronal loss. Since, to date, there is no definitive cure, new therapeutic and prevention strategies are of crucial importance. In this scenario, cannabinoids are deeply investigated as promising neuroprotective compounds for AD. In this study, we evaluated the potential neuroprotective role of cannabinerol (CBNR) in an in vitro cellular model of AD via next-generation sequencing. We observed that CBNR pretreatment counteracts the Aß-induced loss of cell viability of differentiated SH-SY5Y cells. Moreover, a network-based transcriptomic analysis revealed that CBNR restores normal mitochondrial and endoplasmic reticulum functions in the AD model. Specifically, the most important genes regulated by CBNR are related mainly to oxidative phosphorylation (COX6B1, OXA1L, MT-CO2, MT-CO3), protein folding (HSPA5) and degradation (CUL3, FBXW7, UBE2D1), and glucose (G6PC3) and lipid (HSD17B7, ERG28, SCD) metabolism. Therefore, these results suggest that CBNR could be a new neuroprotective agent helpful in the prevention of AD dysfunctions.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Canabinoides , Retículo Endoplasmático , Mitocôndrias , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Canabinoides/farmacologia , Peptídeos beta-Amiloides/metabolismo , Chaperona BiP do Retículo Endoplasmático , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Sobrevivência Celular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Modelos Biológicos , Redes Reguladoras de Genes/efeitos dos fármacos
8.
S Afr J Surg ; 62(2): 71, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38838128

RESUMO

SUMMARY: Cannabis legalisation continues to grow globally and its effects on the vascular system have been scrutinized.1 Cannabis has become recognised as a contributor to cardiovascular, cerebrovascular and peripheral vascular disease.2,3 This case report highlights the case of a young male patient presenting with atypical symptoms following cannabis use who developed gangrenous cholecystitis (GC) following vasospasm of his cystic artery. We believe that this is the first-ever case, shared with the anticipation of stimulating more research and prompting recognition of vascular events in this group of patients as our knowledge on the effects of cannabis continues to grow.


Assuntos
Colecistite Acalculosa , Gangrena , Humanos , Masculino , Gangrena/etiologia , Colecistite Acalculosa/induzido quimicamente , Colecistite Acalculosa/etiologia , Canabinoides/efeitos adversos , Adulto
9.
Ann Plast Surg ; 92(6S Suppl 4): S445-S452, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857012

RESUMO

BACKGROUND: Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand. METHODS: A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate. RESULTS: A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies. CONCLUSION: Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.


Assuntos
Canabinoides , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Vasodilatadores/uso terapêutico , Vasodilatadores/farmacologia , Antifibróticos/farmacologia , Antifibróticos/uso terapêutico , Fibrose/tratamento farmacológico
10.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891938

RESUMO

Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties. Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery. This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies. Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs.


Assuntos
Cannabis , Epilepsia , Doenças Neurodegenerativas , Humanos , Cannabis/química , Doenças Neurodegenerativas/tratamento farmacológico , Epilepsia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Animais , Dor/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Canabinoides/uso terapêutico , Canabinoides/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Analgésicos/uso terapêutico , Analgésicos/química , Analgésicos/farmacologia
11.
Neurotoxicology ; 103: 215-221, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38942151

RESUMO

There is a propensity for synthetic cannabinoid abuse to spread worldwide. CP-55,940, a synthetic cannabinoid having the ability to activate both CB1 and CB2 receptors, has been shown to induce cell death in neurons as well as other cells. Here we investigate molecular events underling the adverse effects of CP-55,940 on neuronal cells. Exposure of mouse neuroblastoma Neuro2a cells to 10-50 µM CP-55,940 results in concentration-dependent cell death that is not accompanied by an induction of apoptosis. CP-55,940 also stimulates autophagy, but the stimulation is not followed by an increase in autophagic degradation. Transcriptome analysis using DNA microarray revealed the increased expression of genes for the cholesterol biosynthesis pathway that is associated with the activation of SREBP-2, the master transcriptional regulator of cholesterol biosynthesis. However, free cholesterol is localized mainly to cytoplasmic structures, although it is localized to the plasma membrane in healthy cells. Thus, cellular trafficking of cholesterol seems to be somewhat disrupted in CP-55,940 stimulated cells. These results show for the first time that CP-55,940 stimulates autophagy as well as cholesterol biosynthesis, although not all the processes involved in the cellular response to CP-55,940 seem to be complete in these cells.


Assuntos
Autofagia , Colesterol , Neurônios , Animais , Camundongos , Colesterol/biossíntese , Colesterol/metabolismo , Autofagia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Linhagem Celular Tumoral , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Canabinoides/toxicidade
12.
Metabolomics ; 20(3): 62, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796627

RESUMO

INTRODUCTION: The chemical classification of Cannabis is typically confined to the cannabinoid content, whilst Cannabis encompasses diverse chemical classes that vary in abundance among all its varieties. Hence, neglecting other chemical classes within Cannabis strains results in a restricted and biased comprehension of elements that may contribute to chemical intricacy and the resultant medicinal qualities of the plant. OBJECTIVES: Thus, herein, we report a computational metabolomics study to elucidate the Cannabis metabolic map beyond the cannabinoids. METHODS: Mass spectrometry-based computational tools were used to mine and evaluate the methanolic leaf and flower extracts of two Cannabis cultivars: Amnesia haze (AMNH) and Royal dutch cheese (RDC). RESULTS: The results revealed the presence of different chemical compound classes including cannabinoids, but extending it to flavonoids and phospholipids at varying distributions across the cultivar plant tissues, where the phenylpropnoid superclass was more abundant in the leaves than in the flowers. Therefore, the two cultivars were differentiated based on the overall chemical content of their plant tissues where AMNH was observed to be more dominant in the flavonoid content while RDC was more dominant in the lipid-like molecules. Additionally, in silico molecular docking studies in combination with biological assay studies indicated the potentially differing anti-cancer properties of the two cultivars resulting from the elucidated chemical profiles. CONCLUSION: These findings highlight distinctive chemical profiles beyond cannabinoids in Cannabis strains. This novel mapping of the metabolomic landscape of Cannabis provides actionable insights into plant biochemistry and justifies selecting certain varieties for medicinal use.


Assuntos
Cannabis , Metabolômica , Folhas de Planta , Cannabis/química , Cannabis/metabolismo , Metabolômica/métodos , Folhas de Planta/metabolismo , Folhas de Planta/química , Flores/metabolismo , Flores/química , Extratos Vegetais/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Canabinoides/metabolismo , Canabinoides/análise , Simulação de Acoplamento Molecular , Flavonoides/metabolismo , Flavonoides/análise , Espectrometria de Massas/métodos
13.
Molecules ; 29(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792027

RESUMO

The aim of our study was to develop a gas chromatographic method coupled with mass spectrometry (GC-MS) for the determination of underivatised neutral (CBDs-N) and acidic (CBDs-A) cannabinoids (CBDs) and cholesterol (Chol). Emphasis was also placed on comparing our original GC-MS method with the currently developed C18-high-performance liquid chromatography with photodiode detection (C18-HPLC-DAD). A combination of a long GC column, shallow temperature column programme, and mass-spectrometry was employed to avoid issues arising from the overlap between CBDs and Chol and background fluctuations. The pre-column procedure for CBDs and Chol in egg yolks consisted of hexane extractions, whereas the pre-column procedure for CBDs in non-animal samples involved methanol and hexane extractions. CBDs-A underwent decarboxylation to CBDs during GC-MS analyses, and pre-column extraction of the processed sample with NaOH solution allowed for CBD-A removal. No losses of CBDs-N were observed in the samples extracted with NaOH solution. GC-MS analyses of the samples before and after extraction with NaOH solution enabled the quantification of CBDs-A and CBDs-N. CBDs-A did not undergo decarboxylation to CBDs-N during C18-HPLC-DAD runs. The use of the C18-HPLC-DAD method allowed simultaneous determination of CBDs-N and CBDs-A. In comparison to the C18-HPLC-DAD method, our GC-MS technique offered improved sensitivity, precision, specificity, and satisfactory separation of underivatised CBDs and Chol from biological materials of endogenous species, especially in hemp and hen egg yolk. The scientific novelty of the present study is the application of the GC-MS method for quantifying underivatised CBDs-A, CBDs-N, and Chol in the samples of interest.


Assuntos
Canabinoides , Colesterol , Cromatografia Gasosa-Espectrometria de Massas , Canabinoides/análise , Canabinoides/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Colesterol/análise , Colesterol/química , Cromatografia Líquida de Alta Pressão/métodos , Animais
14.
Biomed Pharmacother ; 175: 116686, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713939

RESUMO

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety. Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation. In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively. Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method. Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers. For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.


Assuntos
Canabinoides , Dor Crônica , Maconha Medicinal , Neuralgia , Humanos , Masculino , Feminino , Neuralgia/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Canabinoides/farmacocinética , Maconha Medicinal/uso terapêutico , Maconha Medicinal/farmacocinética , Dor Crônica/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Idoso , Estudos de Coortes , Administração por Inalação , Administração Oral , Canabidiol/farmacocinética , Canabidiol/uso terapêutico , Canabidiol/sangue , Espectrometria de Massas em Tandem , Cannabis/química , Adulto Jovem
15.
Braz J Anesthesiol ; 74(4): 844513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38740135

RESUMO

There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.


Assuntos
Canabinoides , Manejo da Dor , Humanos , Canabinoides/efeitos adversos , Canabinoides/uso terapêutico , Brasil , Manejo da Dor/métodos , Anestesiologia , Sociedades Médicas , Técnica Delphi , Dor Aguda/tratamento farmacológico
16.
Int J Nanomedicine ; 19: 4607-4649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799700

RESUMO

Cannabinoids are compounds found in and derived from the Cannabis plants that have become increasingly recognised as significant modulating factors of physiological mechanisms and inflammatory reactions of the organism, thus inevitably affecting maintenance of homeostasis. Medical Cannabis popularity has surged since its legal regulation growing around the world. Numerous promising discoveries bring more data on cannabinoids' pharmacological characteristics and therapeutic applications. Given the current surge in interest in the medical use of cannabinoids, there is an urgent need for an effective method of their administration. Surpassing low bioavailability, low water solubility, and instability became an important milestone in the advancement of cannabinoids in pharmaceutical applications. The numerous uses of cannabinoids in clinical practice remain restricted by limited administration alternatives, but there is hope when biodegradable polymers are taken into account. The primary objective of this review is to highlight the wide range of indications for which cannabinoids may be used, as well as the polymeric carriers that enhance their effectiveness. The current review described a wide range of therapeutic applications of cannabinoids, including pain management, neurological and sleep disorders, anxiety, and cancer treatment. The use of these compounds was further examined in the area of dermatology and cosmetology. Finally, with the use of biodegradable polymer-based drug delivery systems (DDSs), it was demonstrated that cannabinoids can be delivered specifically to the intended site while also improving the drug's physicochemical properties, emphasizing their utility. Nevertheless, additional clinical trials on novel cannabinoids' formulations are required, as their full spectrum therapeutical potential is yet to be unravelled.


Assuntos
Canabinoides , Polímeros , Humanos , Canabinoides/química , Canabinoides/administração & dosagem , Canabinoides/farmacocinética , Canabinoides/farmacologia , Polímeros/química , Sistemas de Liberação de Medicamentos/métodos , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Manejo da Dor/métodos
17.
Biol Res ; 57(1): 33, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802872

RESUMO

BACKGROUND: There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability. METHODS: Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds. RESULTS: The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM. CONCLUSION: Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.


Assuntos
Canabinoides , Cannabis , Caspase 3 , Sobrevivência Celular , Neuroblastoma , Extratos Vegetais , Humanos , Cannabis/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Linhagem Celular Tumoral , Neuroblastoma/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/efeitos dos fármacos , Canabinoides/farmacologia , Canabinoides/química , Caspase 7/metabolismo , Apoptose/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão
18.
J Pharm Biomed Anal ; 245: 116181, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723555

RESUMO

Hemp-sprouts are emerging as a new class of attractive functional food due to their numerous health benefits when compared to other sprout species. Indeed, the high content of beneficial components including polyphenols and flavonoids makes this type of food a promising and successful market. However, the available literature on this topic is limited and often conflicting as regards to the content of phytocannabinoids. High-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS) was applied in an untargeted metabolomics fashion to extracts of hemp seeds, sprouts and microgreens of nine different genotypes. Both unsupervised and supervised multivariate statistical analysis was performed to reveal variety-specific profiles of phytocannabinoids with surprisingly remarkable levels of phytocannabinoids even in chemotype V samples. Furthermore, a targeted HPLC-HRMS analysis was carried out for the quantitative determination of the major phytocannabinoids including CBDA, CBD, CBGA, CBG, CBCA, CBC, THCA, and trans-Δ9-THC. The last part of the study was focused on the evaluation of the enantiomeric composition of CBCA in hemp seeds, sprouts and microgreens in the different varieties by HPLC-CD (HPLC with online circular dichroism). Chiral analysis of CBCA showed a wide variability of its enantiomeric composition in the different varieties, thus contributing to the understanding of the intriguing stereochemical behavior of this compound in an early growth stage. However, further investigation is needed to determine the genetic factors responsible for the low enantiopurity of this compound.


Assuntos
Cannabis , Sementes , Cannabis/química , Cannabis/crescimento & desenvolvimento , Sementes/química , Cromatografia Líquida de Alta Pressão/métodos , Canabinoides/análise , Canabinoides/química , Extratos Vegetais/química , Extratos Vegetais/análise , Espectrometria de Massas/métodos , Metabolômica/métodos , Estereoisomerismo , Dicroísmo Circular/métodos
19.
Molecules ; 29(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38611847

RESUMO

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O' and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes.


Assuntos
Canabidiol , Canabinoides , Cannabis , Células-Tronco Mesenquimais , Extratos Vegetais , Humanos , Canabinoides/farmacologia , Canabidiol/farmacologia , PPAR gama , Endocanabinoides , Tecido Adiposo Marrom , RNA Mensageiro
20.
Rev. ADM ; 81(2): 87-90, mar.-abr. 2024.
Artigo em Espanhol | LILACS | ID: biblio-1561906

RESUMO

Aun cuando las autoridades del Sector Salud en México no se han declarado respecto al uso medicinal de la marihuana, con el objetivo de conocer el estado actual internacional sobre sus riesgos y usos terapéuticos, investigamos los avances reportados en la actualidad, así como las comunidades que han despenalizado su uso. Se presenta su origen como elemento terapéutico, pueblos involucrados, diversas denominaciones, historicidad, las diversas preparaciones, farmacodinamia, sus efectos nocivos a la salud en general y particularmente en boca, sus posibles usos en odontología tomando en cuenta sus propiedades terapéuticas. ampliamente reseñadas en relación a otros lugares del organismo. Finalmente, la propuesta de investigación en odontología con especial énfasis en aquellas especialidades donde la inflamación y el dolor agudo estén presentes de manera significativa (AU)


Although health authorities in Mexico have not officially declared their stance on the medicinal use of marijuana, our research aims to explore the current international status regarding its risks and therapeutic uses. We have investigated the latest reported advancements and examined communities that have decriminalized its usage. This presentation encompasses its therapeutic origin, involved communities, various designations, historical context, diverse preparations, pharmacodynamics, its adverse effects on overall health and particularly oral health, as well as its potential applications in dentistry, considering its widely documented therapeutic properties in comparison to other areas of the body. Finally, our research proposal in dentistry places special emphasis on specialties where inflammation and acute pain are significantly present (AU)


Assuntos
Canabidiol , Cannabis/efeitos adversos , Doenças da Boca/etiologia , Dronabinol/efeitos adversos , Canabinoides/história , Maconha Medicinal/uso terapêutico , Mucosa Bucal/efeitos dos fármacos
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