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ABSTRACT BACKGROUND AND OBJECTIVES: Cannabinoids, such as delta-9-tetrahydrocannabinol and cannabidiol, have several therapeutic properties that may be useful in medicine. The objective of this study was to analyze the impact of cannabinoid use on pain control, quality of life and opioid-sparing in patients with advanced cancer. CONTENTS: A systematic review of the evidence for the use of cannabinoids in patients with advanced cancer was conducted on 1) Pain control; 2) Quality of life; and 3) Opioid-sparing effect. PubMed, Web of Science and Cochrane databases were searched for articles, written in English, published between January 1, 2011, and December 31, 2022, with the filters "randomized controlled trials" and "clinical trials". Using oral formulations of cannabinoids was accepted as "intervention" and placebo as "control". Risk of bias analysis was performed with Cochrane's RoB 2 and ROBINS-I tools. This review followed the 2020 PRISMA- statement. Ten studies were included, with 1169 participants, most with moderate risk of bias. The studies were from Australia (n=4), Canada (n=1), Israel (n=1), Mexico (n=1), The United Kingdom (n=1); two were multinationals. Eight were randomized, placebo-controlled trials; two were non-randomized studies. The most used formulation was nabiximols oral spray. Cannabinoids provide a clinical improvement in pain control. Evidence of improved quality of life with cannabinoids is inconclusive. Cannabinoids do not affect the daily dose of opioids in refractory cancer pain. Cannabinoid use cannot be said to have an opioid-sparing effect. CONCLUSION: It is necessary to expand research on the prescription of cannabinoids in individuals with cancer and other progressive diseases, with several comorbidities and multiple medications, in different health contexts.
RESUMO JUSTIFICATIVA E OBJETIVOS: Os canabinoides, como o delta-9-tetrahidrocanabinol e o canabidiol, possuem propriedades terapêuticas que podem ser úteis em pacientes oncológicos. O objetivo deste estudo foi avaliar o impacto do uso de canabinoides no controle da dor, na melhoria da qualidade de vida, e no efeito poupador de opioides em pacientes com câncer avançado. CONTEÚDO: Realizou-se uma revisão sistemática sobre a evidência da utilização de canabinoides em pacientes com câncer avançado, relativamente a: 1) Controle da dor; 2) Qualidade de vida; e 3) Efeito poupador de opioides. Foram buscados artigos na Pubmed, Web of Science e Cochrane, em inglês, publicados entre 2011 e 2022, com os filtros "randomized controlled trials" e "clinical trials". Aceitaram-se como "intervenção" qualquer uso de formulações orais de canabinoides e como "controle" o uso de placebo. Fez-se análise de viés com as ferramentas da Cochrane RoB 2 e ROBINS-I. Seguiu-se a Declaração PRISMA 2020. Foram incluídos 10 estudos, com 1169 participantes, a maioria com risco moderado de viés. Os estudos provinham de Austrália (n=4), Canadá (n=1), Israel (n=1), México (n=1), Reino Unido (n=1); dois eram multinacionais. Oito eram ensaios randomizados controlados com placebo; dois eram não randomizados. A formulação mais usada foi spray bucal de nabiximóis. Os canabinoides proporcionam uma melhoria clínica do controle da dor. A evidência da melhoria da qualidade de vida com canabinoides é inconclusiva. Os canabinoides não afetam a dose diária de opioides na dor oncológica refratária. Não se pode afirmar que o uso de canabinoides tem um efeito poupador de opioides. CONCLUSÃO: É necessário incrementar a investigação sobre a prescrição de canabinoides em indivíduos com câncer e outras doenças progressivas, com comorbilidades e polimedicação, em diferentes contextos de saúde.
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ABSTRACT The consumption of Cannabis sativa plant, known as marijuana in the Western world, for different purposes (therapeutic, intoxicating, and spiritual) due to its psychoactive effects, can be traced back to ancient times. Cannabis is the most used illicit drug worldwide; however, its legal status is changing rapidly. Cannabis regulation will allow a better understanding of its effects as a misused drug, including new challenges, such as the availability of highly potent Cannabis extracts. Furthermore, scientific research is making significant efforts to take advantage of the potential therapeutic uses of Cannabis active compounds. The science of Cannabis derivatives started with the identification of the phytocannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), allowing the formal study of the complex set of effects triggered by Cannabis consumption and the deciphering of its pharmacology. Δ9-THC is recognized as the compound responsible for the psychoactive and intoxicating effects of Cannabis. Its study led to the discovery of the endocannabinoid system, a neuromodulatory system widespread in the human body. CBD does not induce intoxication and for that reason, it is the focus of the search for cannabinoid potential clinical applications. This review examines the current state of knowledge about contrasting perspectives on the effects of Cannabis, Δ9-THC, and CBD: their abuse liability and potential therapeutic use; two sides of the same coin.
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The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), β-sitosteryl-3-O-β-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-β-D-glucopyranoside(6), phenylethyl-O-β-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-β-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.
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Cannabis , Biological Products , Esters , Dihydrostilbenoids , Plant Components, AerialABSTRACT
Abstract Cannabis sativa L. is one of the most consumed drugs in the world and recent studies have associated its use with an increase in the number of traffic accidents in different countries. In many countries, like Brazil, simple and reliable methodologies are still needed for the detection of drugs on site, mainly cannabinoids, considering its prevalence of use and oral fluid (OF) has been proved as an appropriate biological matrix for this purpose. Considering that, this work aims to review previous studies on immunochromatographic devices for on-site detection of cannabinoids in OF, discussing their sensitivity, specificity, cut-offs values and confirmatory methods. This data shows the importance of choosing a screening device and it reinforces the need for its implementation in Brazil. The research was conducted on 5 databases and all original articles, published in the last 10 years, were selected. A total of 32 articles were found, providing data for 17 screening devices of distinct brands. Only 2 screening devices showed satisfactory sensitivity and specificity in the evaluated studies (≥80% and ≥90% respectively). However, it should be considered that the screening devices still have some limitations, such as a higher cut-off than those recommended by international guidelines (cut-off > 2 ng/mL), therefore demonstrating the need for more studies in the area and the importance of confirmatory analysis usually fulfilled by LC-MS/MS, GC-MS/MS or GC-MS. Thus, the screening analyzes should not be evaluated by itself, but in association with confirmatory results and observational traits (behavioral changes), for a better understanding of the traffic scenario
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Cannabinoids/analysis , Triage/classification , Chromatography, Affinity/instrumentation , Dronabinol/agonists , Cannabis/adverse effects , Accidents, Traffic/prevention & control , Substance Abuse Detection/instrumentationABSTRACT
ABSTRACT Introduction The increasing popularity of cannabinoids for treating numerous neurological disorders has been reported in various countries. Although it reduces tetrahydrocannabinol psychoactivity, it helps patients tolerate higher doses and complements the anti-spasmodic effects of tetrahydrocannabinol. One of the most important potential of cannabinoids are related to its potential to help children with cerebral palsy, a contributor of lifelong disability. Therefore, this systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with cerebral palsy. Methods This review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Seven databases, namely, Scopus, PubMed, EBSCO Host, ProQuest, Google Scholar, Semantic Scholar, and JSTOR, were used to identify relevant studies. Studies examining pediatric patients with cerebral palsy and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. The outcomes of the studies included the efficacy of medical cannabinoids administered for spasticity, motor components, pain control, sleep difficulties, adverse effects, and seizure control. Results Of 803 identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of 133 respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables. Conclusion The anti-spasticity, anti-inflammatory, and anti-seizure properties of cannabinoids might be beneficial for patients with cerebral palsy, although their effectiveness has not been widely studied. Further studies with larger sample sizes and various ethnicities are warranted. Prospero database registration: (www.crd.york.ac.uk/prospero) under ID CRD42022358383.
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ABSTRACT BACKGROUND AND OBJECTIVES: The discovery of the psychoactive agent of Cannabis sativa (tetrahydrocannabinol - THC) in the second half of the 20th century originated the research that later came to identify dozens of other substances from this plant, including cannabinoids, terpenes and flavonoids. Ensuing description of their interaction sites in animals and humans, together with endogenous ligands, transport proteins as well as synthesis and degradation enzymes, revealed what came to be known as the endocannabinoid system. Several receptors participate in this system. CONTENTS: The first receptors to be discovered were called CB1 and CB2, both are G protein-coupled (GPCR). It is noteworthy that CB1 receptors are among the most abundant and widely distributed GPCR in the mammalian brain, with marked expression in basal ganglia, cerebellum and hippocampus, for instance; on the other hand, they are scarce in areas of the brainstem related to breathing control. In light of the multiplicity of pharmacological effects of cannabinoids, concomitant with the lack of more clarifying studies on their mechanisms of action despite the great interest in research on their therapeutic application, it is necessary to deepen the knowledge in this area. CONCLUSION: Considering the literature research conducted for the composition of this article, it is possible to conclude that cannabinoids have a broad spectrum of action mechanisms in the human body, and that more robust clinical studies are needed to better understand their broad therapeutic potential.
RESUMO JUSTIFICATIVA E OBJETIVOS: A descoberta do princípio psicoativo da Cannabis sativa (tetrahidrocanabinol - THC) na segunda metade do século XX inaugurou pesquisas que posteriormente vieram a identificar dezenas de outras substâncias a partir dessa planta, incluindo canabinoides, terpenos e flavonoides. A subsequente descrição dos sítios de interação dessas substâncias em animais e humanos, assim como seus ligantes endógenos, proteínas de transporte e enzimas de síntese e degradação, revelou o que veio a ser conhecido como sistema endocanabinoide. Diversos receptores participam deste sistema. CONTEÚDO: Os primeiros receptores a serem descobertos foram denominados CB1 e CB2, ambos são acoplados à proteína G (GPCR). É importante ressaltar que os receptores CB1 estão entre os GPCRs mais abundantes e amplamente distribuídos do encéfalo de mamíferos, com marcada expressão, por exemplo, em gânglios da base, cerebelo e hipocampo; em contrapartida, são escassos em áreas do tronco cerebral relacionadas ao controle da respiração. Diante da multiplicidade de efeitos farmacológicos dos canabinoides, concomitante à falta de estudos mais esclarecedores sobre seus mecanismos de ação apesar do grande interesse na pesquisa de sua aplicação terapêutica, é preciso aprofundar o conhecimento nessa área. CONCLUSÃO: Considerando as pesquisas bibliográficas realizadas para a composição deste artigo, é possível concluir que os canabinoides possuem um amplo espectro de mecanismos de ação no organismo humano, e que mais estudos clínicos robustos são necessários para que seja possível entender melhor o seu amplo potencial terapêutico.
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ABSTRACT BACKGROUND AND OBJECTIVES: The increasingly widespread use of cannabinoids in the management of acute and chronic pain generates an urgent need to study how cannabinoids act on CB1 and CB2 receptors and what their effects are on the organism. It is important to understand the difference in action between natural cannabinoids (cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, terpenes) and synthetic ones, so that the appropriate choice is made in each case, and depending on the pathophysiology of pain, one or the other active is more indicated. CONTENTS: Studies collected in the Pubmed, Cochrane Library and Web of Science databases were analyzed. These studies focus were on natural cannabinoids (cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, terpenes) and synthetic cannabinoids in the use for the treatment of chronic pain, their action on the endocannabinoid system through the activation of the CB1 and CB2 receptor and their effect after activating this receptor, aiming to compile which cannabinoid is more indicated in the treatment of pain pathology. CONCLUSION: The subject still requires much study and new articles are being published daily. The analysis of the studies must be carried out with criteria to evaluate their seriousness. The endocannabinoid system is closely linked to the treatment of chronic pain and some cannabinoids such as: cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, as well as some terpenes are already considered important in the treatment of chronic pain inferring sparing effect of opioids, anticonvulsants, antidepressants among others.
RESUMO JUSTIFICATIVA E OBJETIVOS: O uso cada vez mais disseminado dos canabinoides no controle da dor aguda e crônica gera uma necessidade urgente do estudo de como os canabinoides agem nos receptores CB1 e CB2 e quais seus efeitos no organismo. É importante entender a diferença de ação entre os canabinoides naturais (canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinol, terpenos) e os sintéticos, para que a escolha adequada seja realizada em cada caso, sendo que dependendo da fisiopatologia da dor é mais indicado um ou outro ativo. CONTEÚDO: Foram analisados estudos coletados na Pubmed, Cochrane Library e Web of Science. Os estudos se concentram em canabinoides naturais (canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinoil, terpenos) e canabinoides sintéticos no uso para o tratamento da dor crônica, sua ação no sistema endocanabinoide através da ativação do receptor CB1 e CB2 e seu efeito após ativar esse receptor, visando compilar qual canabinoide é mais indicado no tratamento da patologia álgica. CONCLUSÃO: O assunto ainda requer muito estudo e diariamente novos artigos vem sendo publicados. A análise dos estudos deve ser realizada com critério para avaliar sua seriedade. O sistema endocanabinoide está intimamente ligado ao tratamento da dor crônica e alguns canabinoides como: canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinoil, assim como alguns terpenos já são considerados importantes no tratamento da dor crônica inferindo efeito poupador de opioides, anticonvulsivantes, antidepressivos entre outros.
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ABSTRACT BACKGROUND AND OBJECTIVES: Cannabis Sativa has been part of human evolution and has been used by different populations for different purposes. By reviewing the history and main advances in cannabinoid medicine, the aim of this study was to identify the major discoveries in recent years, which have prompted the publication of articles. CONTENTS: The following topics were searched: "history of cannabis", "history of hashish", "history of marijuana" and "main advances in endocannabinoid medicine"; in SCIELO, Pubmed, Google Scholar, Brazilian Digital Library of Theses and Dissertations (BDTD), Latin American and Caribbean Literature in Health Sciences (LILACS) and Medline (Capes platform) databases. CONCLUSION: There has been an increase in the number of publications following major discoveries about the endocannabinoid system, including receptors and endocannabinoids, but prejudice and the difficulty of accessing this therapeutic tool prevent further development.
RESUMO JUSTIFICATIVA E OBJETIVOS: A Cannabis Sativa acompanha a evolução humana e foi utilizada por diversas populações para diversos propósitos. Ao revisar a história e os principais avanços na medicina canabinoide, o objetivo deste estudo foi identificar as maiores descobertas nos últimos anos, que fomentaram a publicação de artigos. CONTEÚDO: Os seguintes tópicos foram foram pesquisados: "história da cannabis", "história do haxixe", "história da maconha" e "principais avanços na medicina endocanabinoide"; nos bancos de dados SCIELO, Pubmed, Google Scholar, Biblioteca Digital Brasileira de teses e dissertações (BDTD), Literatura Latino-Americana e do Caribe em Ciências da saúde (LILACS) e Medline (plataforma Capes). CONCLUSÃO: Foi demonstrado o aumento no número de publicações após as grandes descobertas a respeito do sistema endocanabinoide, incluindo os receptores e os endocanabinoides, porém o preconceito e a dificuldade de acesso a essa ferramenta terapêutica impede um maior desenvolvimento.
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ABSTRACT BACKGROUND AND OBJECTIVES: The individualization of treatment has been recognized as essential in medical practice, especially due to the demand for different therapeutic approaches for similar situations. However, the complex and variable nature of the phytocannabinoids present in the cannabis plant presents challenges for the application of traditional models for testing the efficacy and safety of new drugs. The objective of the present study was to highlight the particularities of cannabis, including genetic variety, cultivation and production, which make it difficult to comply with traditional drug registration protocols, and the importance of individualizing treatment in the use of cannabis for the control of pain. CONTENTS: Traditional models for testing the efficacy and safety of new drugs are based on a rigid methodology, divided into development and post-market phases. However, the complexity of the cannabis plant, with hundreds of actives that can vary according to the genetic variety, cultivation and production process, makes the application of these models difficult. In addition, international rules do not allow the registration of patents on cannabis products, due to the consideration that they are natural products and the extraction methods are already used in the industry for other plant actives. The individualization of treatment is fundamental in the use of cannabis for pain control, given the complexity of the plant and the limitations of traditional models of testing and drug registration. CONCLUSION: The particularities of cannabis, such as genetic variability and the impossibility of registering patents, make compliance with current protocols difficult. However, the individualization of treatment allows adapting therapies to the needs of each patient, considering effectiveness and tolerance of side effects. Therefore, there is a need to rethink research and registry models to allow for a more flexible and personalized approach in the field of cannabis medicines.
RESUMO JUSTIFICATIVA E OBJETIVOS: A individualização do tratamento tem sido reconhecida como essencial na prática médica, especialmente devido à demanda por diferentes abordagens terapêuticas para situações semelhantes. No entanto, a natureza complexa e variável dos fitocanabinoides presentes na cannabis apresenta desafios para a aplicação dos modelos tradicionais de testes de eficácia e segurança de novos fármacos. O objetivo deste estudo foi destacar as particularidades da cannabis, incluindo a variedade genética, o cultivo e a produção, que dificultam a conformidade com os protocolos tradicionais de registro de medicamentos, e bem como a importância da individualização do tratamento na utilização da cannabis para o controle da dor. CONTEÚDO: Os modelos tradicionais de testes de eficácia e segurança de novos fármacos são baseados em uma metodologia rígida, dividida em fases de desenvolvimento e pós-mercado. No entanto, a complexidade da planta de cannabis, com centenas de ativos que podem variar de acordo com a variedade genética, o cultivo e o processo de produção, torna difícil a aplicação desses modelos. Além disso, as regras internacionais não permitem o registro de patentes de produtos canábicos, devido à consideração de que são produtos naturais e os métodos de extração já são utilizados na indústria para outros ativos vegetais. A individualização do tratamento é fundamental na utilização da cannabis para o controle da dor, dada a complexidade da planta e as limitações dos modelos tradicionais de testes e registro de fármacos. CONCLUSÃO: As particularidades da cannabis, como a variabilidade genética e a impossibilidade de registro de patentes, dificultam a conformidade com os protocolos atuais. No entanto, a individualização do tratamento permite adaptar as terapias às necessidades de cada paciente, considerando a efetividade e a tolerância aos efeitos colaterais. Portanto, é necessário repensar os modelos de pesquisa e registro para permitir uma abordagem mais flexível e personalizada no campo dos fármacos canábicos.
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RESUMEN El cannabis o marihuana es una de las sustancias psicoactivas más consumida en todo el mundo, por lo que conocer la composición y el tipo de cannabis que se comercializa en los entornos urbanos es un insumo necesario para el diseño de políticas en salud pública sustentadas en la evidencia científica. Este estudio caracterizó los principales fitocannabinoides de muestras de marihuana (cigarrillos o cogollos) obtenidas en áreas urbanas y rurales de la ciudad Medellín, en octubre de 2021. Se realizó un muestreo no probabilístico a conveniencia en el que se recolectaron 87 muestras de marihuana donadas por consumidores en diferentes puntos de recolección en toda la ciudad, aplicando las técnicas de cromatografía de gases masas e ionización de llama para la caracterización de los fitocanabinoides. Se encontró el tetrahidrocannabinol como el constituyente principal de la marihuana circulante en Medellín, donde el 67,8% de las muestras presentaba un rango toxicológico alto o superior para THC; lo anterior en un contexto donde el mercado desregulado limita la posibilidad que tienen los consumidores en la práctica de calibrar o decidir la concentración de cannabinoides en sus dosis.
ABSTRACT As cannabis/marijuana is one of the most consumed psychoactive substances in the world, knowing the composition and type of cannabis sold in urban environments is a necessary input for the design of public health policies based on scientific evidence. This study characterized the main phytocannabinoids of marijuana samples (cigarettes or buds) obtained in urban and rural areas of the city of Medellín in October 2021. Non-probabilistic convenience sampling was carried out in which 87 marijuana samples donated by consumers were collected at different collection points throughout the city, and gas chromatography-mass spectrometry and flame ionization techniques were employed for the characterization of phytocannabinoids. Tetrahydrocannabinol (THC) was found to be the main constituent of circulating marijuana in Medellín, where 67.8% of the samples had a high or higher toxicological range for THC; the foregoing in a context where the deregulated market in practice limits the possibility that consumers have to calibrate or decide the concentration of cannabinoids in their doses.
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ABSTRACT BACKGROUND AND OBJECTIVES: Several studies have shown the growing interest and consumption of cannabinoids and medical cannabis (MC), with management of chronic pain being one of its main therapeutic recommendations. The objective of this study was to review and analyze the results of the most recent preclinical and clinical research on the application of MC and cannabinoids to understand their analgesic efficacy. CONTENTS: A literature review was performed in Pubmed. Preclinical research has shown the role of the endocannabinoid system in pain pathways through the identification of its action sites and pain modulation mechanisms. Numerous clinical studies have endeavored to demonstrate the efficacy of CM and cannabinoids in the management of various pain syndromes. Some international guidelines have already incorporated the use of MC and cannabinoids, but as third or fourth-line treatment and, in most cases, with weak recommendation. CONCLUSION: Despite the growing production of scientific knowledge, the data currently available still lack high-quality evidence to define the efficacy and analgesic potency of cannabinoids. Larger preclinical and clinical research are needed to understand the status of cannabinoids in pain management, as well as to generate high-quality evidence to include or not the use of MC and cannabinoids in guidelines for the management of the various pain syndromes.
RESUMO JUSTIFICATIVA E OBJETIVOS: Diversos trabalhos têm constatado o crescente interesse e o consumo de canabinoides e cannabis medicinal (CM), sendo o auxílio no manejo da dor crônica uma de suas principais indicações terapêuticas na atualidade. O objetivo deste estudo foi revisar e analisar os resultados das mais recentes pesquisas pré-clínicas e clínicas da aplicação da CM e dos canabinoides para compreensão de sua eficácia analgésica. CONTEÚDO: Foi realizada uma revisão de literatura no sistema de busca Pubmed. Pesquisas pré-clínicas têm evidenciado o papel do sistema endocanabinoides nas vias da dor, através da identificação de seus locais de atuação e mecanismos de modulação da dor. Inúmeros estudos clínicos têm mostrado eficácia da CM e dos canabinoides para manejo de diversas síndromes dolorosas. Algumas diretrizes internacionais já incorporaram o uso de CM e canabinoides, mas como tratamento de terceira ou quarta linha e, na maioria dos casos, com poucas recomendações. CONCLUSÃO: Apesar da crescente produção de conhecimento científico, os dados atualmente disponíveis ainda carecem de evidências de alta qualidade para definição da eficácia e poder analgésico dos canabinoides. São necessários maiores estudos pré-clínicos e clínicos para que se possa compreender melhor o status dos canabinoides no manejo da dor, assim como gerar evidências de alta qualidade para incluir ou não o uso da CM e dos canabinoides nos guidelines de manejo das diversas síndromes dolorosas.
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ABSTRACT BACKGROUND AND OBJECTIVES: Prevalence of painful neuropathy is around 7%-10% in the entire population, also, it may have different histories and require integrated care. Challenges for patient care are concerning, most of them have not achieved satisfactory results with drugs for pain management, which are often disabling, in addition to associated comorbidities such as sleep disorders and mood swings. Most of the drugs currently being used for neuropathic pain (NP) have several adverse effects, which hinders adherence to treatment and makes it impossible to reach the doses that would be indicated for proper management. Given this scenario, studies are being done aiming at the endocannabinoid system present in the human body with the ability to modulate pain, sleep, and mood disorders, among other benefits. Drugs such as phytocannabinoids, mainly the molecules cannabidiol (CBD) and tetrahydrocannabidiol (THC), have been studied with significant potential for the treatment of painful neuropathy. This review aimed to describe the probable mechanisms of action of cannabinoids in NP and the results obtained so far with the use of these molecules. CONTENTS: This study is a narrative review of the literature. Data were analyzed using the databases National Library of Medicine (NCBI), Academic Google, Medline and scientific database configurations by LILACS and Web of Science in a temporal search between 2004 and 2022. A total of 45 articles were counted. CONCLUSION: THC modulates opioid effects in neuropathic pain. This is associated with a pharmacokinetic effect and has also been demonstrated by brain imaging. This significant performance can be associated with specific target sites and primary actors regarding Δ-9-THC and its binding to receptors associated with analgesia. Also, further studies with this component or associated with small cannabinoid variations are necessary to certify its role in neuropathic pain.
RESUMO JUSTIFICATIVA E OBJETIVOS: A neuropatia dolorosa tem prevalência estimada em toda a população em torno de 7% a 10%, pode ter diversas etiologias e requer cuidado integrado. O cuidado desses pacientes costuma ser desafiador, pois a maioria deles não obtém resultados satisfatórios com os fármacos disponíveis para manejo da dor que, muitas vezes, são incapacitantes, além das comorbidades associadas, como distúrbios do sono e alterações de humor. A maioria dos fármacos utilizados atualmente para o tratamento da dor neuropática (DN) apresenta diversos efeitos adversos, o que dificulta a adesão ao tratamento e impossibilita atingir as doses que seriam indicadas para o manejo adequado. Diante desse cenário, estudos estão sendo feitos visando o sistema endocanabinoide presente no corpo humano, que tem capacidade de modular a dor, sono e distúrbios do humor, entre outros benefícios. Fármacos como os fitocanabinoides, principalmente com as moléculas canabidiol (CBD) e tetrahidrocanabidiol (THC), têm sido estudados com potencial significativo para o tratamento da neuropatia dolorosa. Esta revisão teve o objetivo de descrever os mecanismos prováveis de ação dos canabinoides na DN e os resultados obtidos até o momento com a utilização dessas moléculas. CONTEÚDO: Este estudo é uma revisão narrativa da literatura. Os dados foram analisados utilizando as bases de dados National Library of Medicine (NCBI), Google acadêmico, Medline e configurações de bases científicas pela LILACS e Web of Science em uma busca temporal entre 2004 e 2022. Foram contabilizados 45 artigos. CONCLUSÃO: O THC modula os efeitos opioides na dor neuropática. Esta atuação é associada com efeito farmacocinético e foi demonstrada por imagens cerebrais. Esta atuação significativa pode ser associada com sítios alvo específicos e atuantes primários com relação ao Δ-9-THC e sua ligação a receptores associados à analgesia. Entretanto, mais estudos com este componente ou associado a pequenas variações canabinoides são necessários para afirmar a sua atuação na dor neuropática.
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ABSTRACT BACKGROUND AND OBJECTIVES: Pharmaceutical preparations of cannabis have been used by mankind since long time ago, and recently they have been the pharmaceutical industry's focus. However, for proper therapeutic application, in-depth knowledge of the endocannabinoid system, which is made mainly by lipid signaling, is needed. The purpose of this study was to explore the current understanding of the players in this system, paying special attention to the molecular machinery required to process it. CONTENTS: This is a narrative review of the current literature regarding major components of the endocannabinoid system, in particular: the receptors, main endogenous ligands, and the enzymes responsible for its components processing. The pharmacological and preclinical aspects were emphasized. CONCLUSION: The better comprehension of the molecular structure of receptors and enzymes will be crucial to developing new pharmacological strategies. A detailed description of the machinery responsible for endocannabinoid lipid metabolization will pave the way for the discovery of new drugs that act on the endogenous system and that can be applied effectively in clinical practice.
RESUMO JUSTIFICATIVA E OBJETIVOS: Os preparados medicinais canabinoides são há muito utilizados pela humanidade e têm sido objeto de interesse da indústria farmacológica recente. Para a aplicação terapêutica adequada é necessário, no entanto, o conhecimento aprofundado do sistema canabinoide endógeno, o qual em sua grande parte é constituído por mensageiros lipídicos. O objetivo deste estudo foi explorar o conhecimento vigente a respeito dos constituintes desse sistema, com especial atenção à maquinaria molecular necessária para processá-los. CONTEÚDO: Trata-se de uma revisão narrativa da literatura atual acerca dos integrantes do sistema canabinoide endógeno, notadamente: seus receptores, os principais ligantes endógenos e as enzimas responsáveis pelo processamento de seus componentes. Os aspectos farmacológicos e pré-clínicos foram enfatizados. CONCLUSÃO: O melhor entendimento da ultraestrutura de receptores e enzimas contribuirá de forma decisiva para o desenvolvimento de novas estratégias farmacológicas. A partir da descrição pormenorizada da maquinaria responsável pela metabolização lipídica endocanabinoide é que se pavimentará o caminho para a descoberta de novos fármacos que atuem no sistema endógeno e que possam ser aplicados de forma eficaz na prática clínica.
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ABSTRACT BACKGROUND AND OBJECTIVES: Pain is "an unpleasant sensory and emotional experience associated or not with real or potential tissue damage" which, when exceeding its protective function, beyond three months, is considered chronic pain, which in the long term can have its own clinical course. Given the scientific advances on the therapeutic effects of cannabinoids, the article brings a proposal for reflection as the Brazilian public health system (SUS - Sistema Único de Saúde), through medical cannabis, could offer better therapies for the treatment of conditions such as chronic pain. CONTENTS: A narrative review was elaborated in databases such as Pubmed, Medline and Scielo. Considering the SUS Guidelines, the incorporation and access to medicinal cannabis can be understood as a strategy of social justice and reduction of inequities, because it is effective and safe in the treatment of chronic conditions, besides that the system already has strategies and policies aimed at regulating and distributing herbal medicines. Chronic pain is a prevalent condition, affects more than 2 billion people worldwide, and can be considered a global crisis. In Brazil, its prevalence varies between 23.02% and 76.17%, being higher in the elderly and female individuals. Despite this, in many cases, conventional treatments do not generate the analgesics effects expected, in addition to causing important adverse effects. CONCLUSION: Cannabis sativa L. has great potential to become one of the best alternatives for chronic pain to be incorporated into herbal access programs around the country, such as in the SUS' Farmácia Viva project.
RESUMO JUSTIFICATIVA E OBJETIVOS: A dor é "uma experiência sensitiva e emocional desagradável associada ou não a uma lesão tecidual real ou potencial" que ao exceder sua função de proteção, além de três meses, é considerada dor crônica, que à longo prazo pode ter seu próprio curso clínico. Diante dos avanços científicos acerca dos efeitos terapêuticos dos canabinoides, este artigo traz uma proposta de reflexão sobre como o Sistema Único de Saúde (SUS), por meio da medicina canábica, poderia ofertar melhores terapêuticas para o tratamento de condições que cursam com dor crônica. CONTEÚDO: Foi elaborada uma revisão narrativa em bancos de dados como Pubmed, Medline e Scielo. Considerando as diretrizes do SUS, a incorporação e acesso a cannabis medicinal pode ser entendida como estratégia de justiça social e redução de inequidades, por ser eficaz e segura no tratamento de condições crônicas, além de que o sistema já conta com estratégias e políticas voltadas para regulamentação e distribuição de fitoterápicos. Dor crônica é uma condição prevalente, afeta mais de 2 bilhões de pessoas em todo o mundo e pode ser considerada uma crise global. No Brasil, sua prevalência varia entre 23,02% e 76,17%, sendo maior em idosos e em pessoas do sexo feminino. Apesar disso, em muitos casos, os tratamentos convencionais não geram os efeitos analgésicos esperados, além de causarem efeitos adversos importantes. CONCLUSÃO: A Cannabis sativa L. tem um grande potencial de se tornar uma das melhores alternativas para dor crônica a ser incorporada nos programas de acesso a fitoterápicos no país, como no programa Farmácia Viva, do SUS.
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ABSTRACT BACKGROUND AND OBJECTIVES: The use of cannabinoids for epileptic syndrome and control of side effects associated with chemotherapy is already widespread and supported by several well-controlled clinical trials. However, the use of these drugs in inflammatory pathologies is sometimes underestimated due to lack of scientific knowledge with a high degree of evidence, non-recognition of the endocannabinoid system as an active participant in these diseases, as well as fear of the stereotype surrounding the use of cannabis derivatives. The purpose of this study was to examine the anti-inflammatory and antioxidant effects of endogenous and exogenous cannabinoids on various physiological systems in which these ligands interact. CONTENTS: Studies cited in this review were obtained by searching Pubmed, Medline, Google Scholar, Scielo, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and through the authors' familiarity with the published literature in this area of interest. Clinical, observational and intervention, experimental, qualitative studies and review articles were all included in the search. Articles were identified using the following descriptors: cannabis and tetrahydrocannabinol and cannabidiol and endocannabinoids and anti-inflammatory inflammation and oxidative stress. In addition, a manual revision of relevant references was also performed to capture articles that may not have been picked up through the initial search. The literature investigation was conducted from March 22 to May 2022. CONCLUSION: Cannabinoids show to be a promising therapeutic option in the context of inflammatory diseases, given the complete and complex relationship between the endocannabinoid system and the immune system. The setback to be overcome in the use of cannabinoids as anti-inflammatory drugs includes the synthesis of non-psychoactive cannabinoid receptor agonists while maintaining potent anti-inflammatory activity. Further studies are needed to increase our understanding of cannabinoids and their intricate effects on immune system disorders.
RESUMO JUSTIFICATIVA E OBJETIVOS: O uso de canabinoides para síndrome epiléptica e controle de efeitos adversos associados à quimioterapia já é amplamente difundido e apoiado por vários ensaios clínicos bem controlados. Entretanto, o uso destes fármacos em doenças inflamatórias é, por vezes, subestimado pela falta de conhecimento científico com alto grau de evidência, pelo não reconhecimento do sistema endocanabinoide como participante ativo destas doenças, bem como por receio do estereótipo que envolve o uso dos derivados da cannabis. O objetivo deste estudo foi analisar os efeitos anti-inflamatórios e antioxidantes de canabinoides endógenos e exógenos em vários sistemas fisiológicos nos quais esses ligantes interagem. CONTEÚDO: Estudos citados nesta revisão foram obtidos por meio de buscas feitas nas bases de dados Pubmed, Medline, Google Acadêmico, Scielo, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, e através da familiaridade dos autores com a literatura publicada nesta área de interesse. Estudos clínicos, observacionais e de intervenção, experimentais, qualitativos e artigos de revisão foram todos incluídos na pesquisa. Os artigos foram identificados usando os seguintes descritores: cannabis , tetraidrocanabinol e canabidiol e endocanabinoides e inflamação anti-inflamatório e estresse oxidativo. Ademais, uma revisão manual nas referências relevantes também foi realizada para captura de artigos que podem não ter sido captados por meio da busca inicial. A investigação na literatura foi realizada no período de 22 de março a 17 de maio de 2022. CONCLUSÃO: Os canabinoides demonstram ser uma opção terapêutica promissora no contexto das doenças inflamatórias, haja vista a completa e complexa relação entre o sistema endocanabinoide e o sistema imune. O revés a ser vencido no uso de canabinoides como fármacos anti-inflamatórios inclui a síntese de agonistas de receptores canabinoides que não sejam psicoativos, mantendo a potente atividade anti-inflamatória. Novos estudos são necessários para aumentar a compreensão dos canabinoides e seus efeitos intrincados sobre distúrbios do sistema imunológico.
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ABSTRACT BACKGROUND AND OBJECTIVES: Spasticity refers to the increase of resistance to joint passive movement according to its angular velocity. It is part of the triad of the pyramidal syndrome, along with the exacerbation of myotatic reflexes and muscle weakness, and is present in several lesions of the central nervous system, either in the spinal cord or brain. Pain associated with spasticity is caused by muscle spasms, activation of trigger points, joint deformities, interference with the position of body segments, and difficulty in movement control. For a more precise therapeutic intervention, the detailed physical examination of the locomotor system and spasticity can be completed by using specific spasticity evaluation scales. Multiple sclerosis (MS) is the clinical condition for which there are the greatest number of studies using cannabi-noids to control spasticity. The objective of this study was to perform a literature review of the possible role of cannabinoid drugs in the control of spasticity and the pain associated with it. CONTENTS: The literature shows moderate evidence that the combined use of 9-tetrahydrocannabinol and cannabidiol increases the number of people reporting improvement in spasticity. CONCLUSION: It is possible to believe that the complaint of musculoskeletal pain associated with spasticity accompanies this improvement with the use of nabiximols, but there are still gaps in the literature for this specific topic.
RESUMO JUSTIFICATIVA E OBJETIVOS: A espasticidade refere-se ao aumento da resistência ao movimento passivo articular conforme a sua velocidade angular. Ela faz parte da tríade da síndrome piramidal, junto com a exacerbação de reflexos miotáticos e fraqueza muscular, e está presente em diversas lesões do sistema nervoso central, de topografia medular ou encefálica. A dor associada à espasticidade é causada pelos espasmos musculares, ativação de pontos-gatilho, deformidades articulares, interferência na posição dos segmentos corporais e dificuldade para o controle do movimento. Para uma intervenção terapêutica mais precisa, o exame físico detalhado do aparelho locomotor e da espasticidade pode ser completado pelo uso de escalas de avaliação específicas. A esclerose múltipla é a condição clínica para a qual há maior número de estudos com uso de canabinoides para o controle da espasticidade. O objetivo deste estudo foi realizar uma revisão da literatura sobre o possível papel dos fármacos canabinoides no controle da espasticidade e da dor associada a ela. CONTEÚDO: Há na literatura evidências moderadas de que o uso combinado de 9-tetrahidrocanabinol e canabidiol aumenta o número de pessoas que relatam melhora da espasticidade. CONCLUSÃO: É possível acreditar que a queixa de dor musculoesquelética associada à espasticidade acompanhe essa melhora com uso de nabiximol, mas ainda há lacunas na literatura para esse tópico específico.
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ABSTRACT BACKGROUND AND OBJECTIVES: Evidence has highlighted a role of glial cell activation, and their interaction with different neural systems, especially the endocannabinoid system, in the mechanisms involved in the chronicity and maintenance of pain. The aim of this review is to bring an update on published data that demonstrate the interaction between glial cells and the endocannabinoid system in the pathophysiology of chronic pain and its treatment. CONTENTS: A narrative review was performed based on a research in the Medline database, using the Keywords "endocannabinoid", "glial cells", "microglial", "astrocytes", "neuroinflammation". CONCLUSION: Deepening the knowledge about the function of glial cells in the endocannabinoid system will open the possibility of acting on the pathophysiological origin of the pain chronification process, attenuating the mechanisms involved in central sensitization.
RESUMO JUSTIFICATIVA E OBJETIVOS: A evidência científica tem ressaltado um papel da ativação das células da glia e de sua interação com diversos sistemas neurais, com destaque para o sistema endocanabinoide e mecanismos envolvidos na cronificação e manutenção da dor. O objetivo deste estudo foi atualizar os dados publicados que mostrem a interação entre as células da glia com o sistema endocanabinoide na fisiopatologia da dor crônica e seu tratamento. CONTEÚDO: Foi realizada uma revisão narrativa baseada em pesquisa na base de dados Medline, com uso dos unitermos "endocannabinoid", "glial cells", "microglial", "astrocytes", "neuroinflammation". CONCLUSÃO: O aprofundamento do conhecimento acerca da função das células da glia no sistema endocanabinoide abrirá a possibilidade de atuação sobre a origem fisiopatológica do processo de cronificação de dor, atenuando os mecanismos envolvidos na sensibilização central.
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Introdução: A periodontite é um importante problema de saúde pública. Embora o princípio da terapia da periodontite esteja focado principalmente na remoção do biofilme dental e dos fatores associados, sua fisiopatologia registra diferentes eventos moleculares e inflamatórios relacionados ao sistema imunológico do hospedeiro, como a participação do sistema endocanabinoide. Objetivo: Esta revisão teve como objetivo explorar e elucidar os mecanismos e papéis do sistema endocanabinoide na fisiopatologia da periodontite e suas possibilidades para futuras terapias relacionadas. Material e método: Realizou-se uma busca eletrônica na plataforma PubMed por estudos envolvendo a ação do sistema endocanabinoide sobre a periodontite. Resultado: Dezenove estudos clínicos e pré-clínicos foram incluídos nesta revisão narrativa. Conclusão: Os receptores canabinoides tipo 1 e 2 são componentes integrais do sistema endocanabinoide e manifestam-se de várias formas nos tecidos periodontais. As ações e mecanismos através dos quais os receptores canabinoides são ativados em locais saudáveis ou inflamados continuam a ser o foco de investigações em curso. Além disso, os fitocanabinoides e canabinoides sintéticos apresentam potencial como tratamentos, com estudos pré-clínicos indicando benefícios na redução da inflamação e na facilitação da reparação dos tecidos.
Introduction: Periodontitis is a major public health problem. Although the principle of periodontitis therapy is mainly focused on removing dental biofilm and associated factors, its physiopathology enrolls different molecular and inflammatory events related to the host immune system, as the participation of the endocannabinoid system. Objective: This review aimed to explore and elucidate the mechanisms and roles of the endocannabinoid system on periodontitis physiopathology and its possibilities for future related therapies. Material and method: An electronic search was carried out on the PubMed platform for studies involving the action of the endocannabinoid system on periodontitis. Result: Nineteen clinical and preclinical studies were included in this narrative review. Conclusion: Cannabinoid receptors type 1 and 2 are integral components of the endocannabinoid system, manifesting in various forms in the periodontal tissues. The actions and mechanisms through which cannabinoid receptors are activated in healthy or inflamed sites remain the focus of ongoing investigations. Moreover, phytocannabinoids and synthetic cannabinoids show therapeutic potential, with pre-clinical studies indicating benefits in reducing inflammation and facilitating tissue repair
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Periodontitis/physiopathology , Cannabinoids , Public Health , Receptor, Cannabinoid, CB1 , Receptor, Cannabinoid, CB2 , InflammationABSTRACT
A group of compounds structurally related to tetrahydrocannabinol or capable of binding to cannabinoid receptors are collectively referred to as cannabinoids. Cannabinoids can be divided into plant derived cannabinoids， synthetic cannabinoids， and endogenous cannabinoids. Δ-9-THC is the only psychoactive compound in plant cannabinoids. Cannabis with Δ-9-THC>0.3% is internationally listed as a prohibited drug， while cannabis with Δ-9-THC<0.3% is industrial cannabis. Due to its low addiction and high commercial value， it is allowed to be added to food in many countries. More and more industrial cannabis foods become popular， and the detection/analysis of cannabinoid compounds in cannabis foods is particularly important； In addition to industrial cannabis， which is widely used in food， there are also various new drugs， synthetic cannabinoids， disguised as conventional food， which can cause the social problems and increase the food safety risks. This article will elaborate on the regulatory status of cannabinoid compounds in food， In order to promote the safety supervision of the domestic cannabis food.
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El cannabis se ha utilizado desde la antigüedad con fines recreativos y medicinales. Es una fuente muy rica de compuestos químicos, la mayoría denominados fitocannabinoides, que tienen una variedad de efectos fisiológicos, principalmente por su unión a receptores cannabinoides endógenos como el CB1 y CB2, entre otros. El cannabis tiene propiedades terapéuticas potenciales y sus preparaciones se han utilizado como remedios tradicionales para tratar el dolor y la emesis. Los cannabinoides sintéticos se utilizan clínicamente como analgésicos, antiespasmódico, antieméticos y estimulantes del apetito. La toxicidad significativa del cannabis es poco común en los adultos, sin embargo, puede tener múltiples efectos adversos agudos y crónicos. La calidad de la evidencia en este campo se ha visto limitada por la corta duración de los estudios, los reducidos tamaños de las muestras, la falta de grupos de control y la existencia de sesgos en la mayoría de los estudios revisados. En este contexto, son necesarios más estudios de mejor calidad metodológica para apoyar el uso seguro de esta terapia en otras enfermedades. La decisión de incorporar los cannabinoides como terapia en alguna de las condiciones descritas depende de la evidencia, el uso de terapias previas y el tipo de paciente.
Since ancient times cannabis has been used for recreational and medicinal purposes. It is a significant source of chemical compounds, most of them called phytocannabinoids. These compounds have several physiological effects and produce their effects primarily by binding to endogenous cannabinoid receptors such as CB1 and CB2, among others. Cannabis has potential therapeutic properties and its preparations have been used as traditional remedies to treat pain and emesis. Synthetic cannabinoids are used clinically as analgesics, antispastics, antiemetics, and appetite stimulants. Significant cannabis toxicity is rare in adults; however, it can produce countless acute and chronic side effects. The quality of the evidence in this field is limited by the short duration of the trials, poor sample sizes, lack of a control group, and the existence of bias in most of the reviewed studies. Therefore, a larger number of studies with better methodological quality is required to support the safe use of this therapy. The decision to include cannabinoids as a treatment for any of the conditions described will depend on the evidence, the use of previous therapies, and the type of patient.