Neuroprotective potential of cannabidiol: Molecular mechanisms and clinical implications / 中西医结合学报

Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.

O uso do canabidiol em crianças com epilepsia resistente a medicamento e a diminuição na frequência das crises: revisão rápida / The use of cannabidiol in children with drug-resistant epilepsy and the decrease in the frequency of seizures: quick review

Uso de canabidiol (CDB) medicinal presente no óleo de canabis. Indicação: Tratamento de crianças portadoras de epilepsia refratária resistente a medicação e síndromes graves decorrentes. Pergunta: O uso do canabidiol em crianças com epilepsia resistente a medicamentos apresentaria diminuição na frequência de crises convulsivas? Objetivo: Investigar a eficácia e a segurança do canabidiol, em comparação a placebo, na manutenção da remissão em crianças com epilepsia refratária. Métodos: Revisão rápida de revisões sistemáticas, por meio de buscas bibliográficas realizadas nas bases PUBMED, SCOPUS, BVS, Cochrane Library. Foram utilizadas estratégias de buscas com vocabulário padronizado e avaliação da qualidade metodológica usando o checklist AMSTAR 2. Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade. O CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria (RR 1.69 [1.20 ­ 2.36]), para a síndrome de Lennox-Gastaut o RR foi 2.98 (IC 95%, 1.83 - 4.85) e para a síndrome de Dravet o RR foi 2.26 (IC 95% ,1.38 - 3.70). O CDB pode resultar em uma diminuição no apetite em dosagens maiores (RR = 2,10, IC 95% [0,96­4,62], embora não apresente diferença de efeito dos grupos comparadores. Conclusão: Duas revisões sistemáticas recentes o CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria e síndromes graves. Entretanto, existem poucos ensaios clínicos publicados na área

: Use of cannabidiol (CBD) present in cannabis oil. Indication: Treatment of children with drug-resistant refractory epilepsy and severe syndromes resulting. Question: Would the use of cannabidiol in children with drug-resistant epilepsy lead to a decrease in seizure frequency? Objective: to investigate the efficacy and safety of cannabidiol, compared to placebos, in maintaining remission in children with refractory epilepsy. Methods: Rapid review of systematic reviews, through a bibliographical search carried out in the PUBMED, SCOPUS, BVS, Cochrane Library databases. Predefined search strategies were followed, and the methodological quality of the included studies was evaluated using the AMSTAR 2 tool. Results: Two systematic reviews were selected, which met the eligibility criteria. CBD when compared to placebo reduce 50% of seizures for refractory epilepsy (RR 1.69, IC 95% [1.20 ­ 2.36]), for Lennox-Gastaut Syndrome the RR was foi 2.98 (IC 95%, 1.83 - 4.85) and for Dravet Syndrome o RR FOI 2.26 (IC 95% ,1.38 - 3.70). CBD may result in appetite decrease using high doses (RR = 2.10, 95% IC [0.96­ 4.62], with no statistical difference. Conclusion: Two recent systematics, CBD, when compared to placebo, presented 50% of seizures for refractory epilepsy and severe syndromes. However, there are few clinical trials published in the area

Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation / 中西医结合学报

Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient's life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects. Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells. Cannabinoids promote atypical protein kinase C, deactivate fatty acid amide hydrolase enzymes, and activate transient receptor potential vanilloid 1 (TRPV1) and TRPV2 to induce pro-apoptotic signaling pathways without increasing endogenous cannabinoids. In previous in vivo studies, endocannabinoids, chemically classified as amide formations of oleic and palmitic acids, have been shown to increase the pro-apoptotic activity of human cancer cells and inhibit cell migration and angiogenesis. This review focuses on the biological synthesis and pharmacology of endogenous cannabinoids for the enhancement of cancer cell apoptosis, which have potential as a novel therapy for GBM. Please cite this article as: Duzan A, Reinken D, McGomery TL, Ferencz N, Plummer JM, Basti MM. Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation. J Integr Med. 2023; 21(2): 120-128.

O emprego da Cannabis medicinal no enfrentamento à doenças / The use of medicinal Cannabis in fighting diseases

A Cannabis possui como subespécie a Cannabis sativa. As plantas do gênero Cannabis possuem propriedades terapêuticas que são oriundas de compostos denominados canabinoides. O objetivo do presente artigo foi evidenciar como procede o uso terapêutico da Cannabis para enfrentamento das doenças. Realizou-se revisão narrativa da literatura com busca nas bases de dados: PubMED, Google Acadêmico com levantamento de artigos que tratavam acerca do uso da Cannabis medicinal para o tratamento de algumas doenças. Canabinoides correlacionam-se a receptores do nosso corpo, influindo nos mecanismos que regulam o organismo. Cannabis possibilita abordar e intervir em determinadas patologias presentes nos pacientes advindo de possuir ações benéficas anticonvulsivantes, anti-inflamatórias, analgésicas, ansiolíticas, antipsicóticas e antitumorais. Em nosso corpo existem os canabinoides ou endocanabinoides, que são similares aos canabinoides naturais ou fitocanabinoides estruturados na Cannabis. O canabidiol e o tetra-hidrocarbinol constituem canabinoides provenientes da Cannabis que podem tecer relação com os canabinoides configurados por nosso próprio corpo. O sistema de endocanabinoides possibilitou averiguar-se acerca do emprego do canabidiol para tratamento de patologias, como: Doença de Parkinson, Autismo e Epilepsia. Concluiu-se que o emprego terapêutico da Cannabis medicinal pode representar recurso que será válido para resolução do problema de saúde, podendo propiciar melhores condições e qualidade de vida aos pacientes portadores de determinadas patologias em que essa droga pode ser utilizada para tratamento.

Cannabis has Cannabis sativa as a subspecies. Cannabis plants have therapeutic properties that come from compounds called cannabinoids. The aim of this article was to show how the therapeutic use of Cannabis to cope with diseases proceeds. A narrative review of the literature was carried out with a search in the following databases: PubMED, Google Scholar with a survey of articles that dealt with the use of medicinal Cannabis for the treatment of some diseases. Cannabinoids correlate to our body's receptors, influencing the mechanisms that regulate the body. Cannabis makes it possible to address and intervene in certain pathologies present in patients arising from having beneficial anticonvulsant, anti-inflammatory, analgesic, anxiolytic, antipsychotic and antitumor actions. In our body there are cannabinoids or endocannabinoids, which are similar to natural cannabinoids or phytocannabinoids structured in Cannabis. Cannabidiol and Tetrahydrocannabinol are cannabinoids derived from Cannabis that can be related to cannabinoids configured by our own body. The endocannabinoid system made it possible to investigate the use of cannabidiol for the treatment of pathologies, such as: Parkinson's Disease, Autism and Epilepsy. It was concluded that the therapeutic use of medicinal Cannabis can represent a resource that will be valid for solving the health problem, providing better conditions and quality of life for patients with certain pathologies in which this drug can be used for treatment.

Uso terapêutico da cannabis medicinal em pessoas com doença neurológica degenerativa / Therapeutic use of medicinal cannabis in people with degenerative neurological disease / Uso terapéutico de cannabis medicinal en personas con enfermedad neurológica degenerativa

Objetivo: apresentar o estado da arte das publicações expressas na literatura cientifica mundial sobre a temática, bem como identificar os benefícios terapêuticos da Cannabis medicinal no tratamento dos sintomas das doenças neurodegenerativas especificamente doenças de Parkinson, esclerose múltipla e Alzheimer. Método: trata-se de uma revisão integrativa da literatura, cuja busca de dados foi realizada nas bibliotecas virtuais. Web of Science, Scopus, Medline, Lilacs, Cochrane Library e Scielo no período de agosto a outubro de 2021. Resultados: foram encontrados 158 artigos. Vinte e tres artigos foram selecionados para serem lidos na íntegra e 8 atenderam aos critérios desta revisão. Conclusão: as evidências mostram que embora cada vez mais prescritos ou autorizados, a cannabis medicinal ou os Canabinóides para a doenças neurodegenerativas continuam a ser controversos para muitos médicos.

Objective: to present the state of the art of publications expressed in the world Scientific literature on the subject, as well as to identify the therapeutic benefits of medicinal cannabis in the treatment of neurodegenerative diseases, specifically, Parkinson's diseases, multiple sclerosis and Alzheimer's. Method: this is an integrative literature review, whose data search was performed in virtual librares. Web of Science, Scopus, Medline, Lilacs, Cochrane Library and Scielo from August to October 2021. Results:158 articles were found. Twenty-three articles were selected to be read in full and 8 met the criteria of this review. Conclusion: evidence shows that although increasingly prescribed or authorized, medical cannabis or Cannabinoids for chronic pain remain controversial for many physicians.

Objetivo: presentar el estado del arte de las publicaciones expresadas en la literatura científica mundial sobre el tema, así como identificar los beneficios terapéuticos del cannabis medicinal en el tratamiento de enfermedades neurodegenerativas, en concreto, las enfermedades de Parkinson, la esclerosis múltiple y el Alzheimer. Método: se trata de una revisión integradora de la literatura, cuya búsqueda de datos se realizó en bibliotecas virtuales. Web of Science, Scopus, Medline, Lilacs, Cochrane Library y Scielo de agosto a octubre de 2021. Resultados: se encontraron 158 artículos. Se seleccionaron veintitrés artículos para ser leídos en su totalidad y ocho cumplieron los criterios de esta revisión. Conclusión: la evidencia muestra que, aunque cada vez más se prescribe o autoriza, el cannabis medicinal o los cannabinoides para el dolor crónico siguen siendo controvertidos para muchos médicos.

Benefícios terapêuticos dos canabinoides no tratamento da dor crônica em pacientes com câncer / Therapeutic benefits of cannabinoids in the treatment of chronic pain in cancer patients / Beneficios terapéuticos del cannabinoides en el tratamiento del dolor crónico en pacientes con cáncer

Objetivo: apresentar o estado da arte das publicações expressas na literatura cientifica mundial sobre a temática, bem como identificar os benefícios terapêuticos da Cannabis medicinal no tratamento da dor. Método: trata-se de uma revisão integrativa da literatura, cuja busca de dados foi realizada nas bibliotecas virtuais. Web of Science, Scopus, Medline, IBECS, Lilacs, Cochrane Library, Emerald Insight e Scielo no período de agosto a outubro de 2021. Resultados: foram encontrados 367 artigos. Quarenta e três artigos foram selecionados para serem lidos na íntegra e 15 atenderam aos critérios desta revisão. Conclusão: as evidências mostram que embora cada vez mais prescritos ou autorizados, a cannabis medicinal ou os Canabinóides para a dor crónica continuam a ser controversos para muitos médicos.

Objective: to present the state of the art of publications expressed in the world scientific literature on the subject, as well as to identify the therapeutic benefits of medicinal cannabis in the treatment of pain. Method: this is an integrative literature review, whose data search was performed in virtual libraries. Web of Science, Scopus, Medline, IBECS, Lilacs, Cochrane Library, Emerald Insight and Scielo from August to October 2021. Results: 367 articles were found. Forty-three articles were selected to be read in full and 15 met the criteria of this review. Conclusion: evidence shows that although increasingly prescribed or authorized, medical cannabis or Cannabinoids for chronic pain remain controversial for many physicians.

Objetivo: presentar el estado del arte de las publicaciones expresadas en la literatura científica mundial sobre el tema, así como identificar los beneficios terapéuticos del cannabis medicinal en el tratamiento del dolor. Método: se trata de una revisión integradora de la literatura, cuya búsqueda de datos se realizó en bibliotecas virtuales. Web of Science, Scopus, Medline, IBECS, Lilacs, Cochrane Library, Emerald Insight y Scielo de agosto a octubre de 2021. Resultados: se encontraron 367 artículos. Se seleccionaron 43 artículos para ser leídos en su totalidad y 15 cumplieron con los criterios de esta revisión. Conclusión: la evidencia muestra que, aunque cada vez más se prescribe o autoriza, el cannabis medicinal o los cannabinoides para el dolor crónico siguen siendo controvertidos para muchos médicos.

Cannabis. Usos y aplicaciones en la práctica odontológica diaria: revisión de la literatura / Cannabis. Uses and applications in daily dental practice: a review of the literature

La evidencia científica presente en la literatura indica que el cannabis puede ser utilizado con fines terapéuticos para tratar distintas afecciones odontológicas. Dado el acceso sencillo a la cavidad bucal, las distintas formulaciones de cannabis pueden aplicarse de forma tópica. La aplicación local de dosis bajas de cannabis ha demostrado alta efectividad para tratar distintas afecciones bucales, constituyendo un tratamiento seguro con baja probabilidad de generar repercusiones sistémicas indeseadas. En la actualidad, está siendo incorporado a materiales convencionales de uso e higiene odontológica con la finalidad de aprovechar sus efectos terapéuticos. El cannabis tiene múltiples usos en odontología: como componen-te de enjuagues bucales y soluciones para la desinfección de conductos radiculares, en tratamientos de trastornos de ansiedad bucal, como complemento en terapias oncológicas, como analgésico para atenuar el dolor inflamatorio y el neuropático, como miorrelajante y condroprotector para tratar trastornos de articulación témporomandibular (ATM) y bruxismo, como osteomodulador para el tratamiento de patologías que comprometen la integridad ósea, como la enfermedad periodontal y la osteoporosis, y para la cicatrización ósea asociada a fracturas, extracciones dentarias e implantes, y como inmunomodulador con potencial terapéutico para tratar patologías autoinmunes como las enfermedades reumáticas. El trata-miento local con cannabis es efectivo, bien tolerado por el paciente y con pocos efectos adversos. Por lo tanto, se puede concluir que el cannabis aporta un enorme abanico de posibilidades terapéuticas para tratar distintas afecciones odontológicas, aunque aún se requiere mayor cantidad de estudios científicos que avalen su utilización en cada situación fisiopatológica particular (AU)

The scientific evidence present in the literature indicates that cannabis can be used for therapeutic purposes to treat different dental conditions. Given the easy access to the oral cavity, the different cannabis formulations can be applied topically. The local application of low doses of cannabis has shown high effectiveness in treating different oral conditions, constituting a safe treatment with a low probability of generating unwanted systemic repercussions. It is currently being incorporated into conventional materials for dental use and hygiene in order to take advantage of its therapeutic effects. Cannabis has multiple uses in dentistry: as a component of mouthwashes and solutions for disinfecting root canals, in the treatment of oral anxiety disorders, as a complement in oncological therapies, as an analgesic to reduce inflammatory and neuropathic pain, as a muscle relaxant and chondroprotective to treat temporomandibular joint disorders and bruxism, as an osteomodulator for the treatment of pathologies that compromise bone integrity, such as periodontal disease and osteoporosis, and or bone healing associated with fractures, dental extractions and implants, and as immunomodulator with therapeutic potential to treat autoimmune pathologies such as rheumatic diseases. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Therefore, it can be concluded that cannabis provides an enormous range of therapeutic possibilities to treat different dental conditions, although more scientific studies are still required to support its use in each particular pathophysiological situation (AU)

Situación actual de Cannabis sativa, beneficios terapéuticos y reacciones adversas / Current status of Cannabis sativa; therapeutic benefits and adverse reactions

Introducción: En la actualidad, uno de los temas más polémicos que involucra en gran proporción al campo de la Medicina es el uso terapéutico de la marihuana y su legalización. Esta planta de reconocimiento milenario ha desatado en las últimas décadas disímiles de controversias dado el descubrimiento del sistema endocannabinoide que revolucionó la investigación sobre ella. Objetivo: Describir la situación actual del cannabis, sus beneficios terapéuticos y sus efectos adversos. Material y métodos: Se realizó una exhaustiva búsqueda y revisión empleando los Descriptores en Ciencias de la Salud, en idioma inglés y español, consultando las bases de datos Pubmed, Scielo, Lilacs, Cochrane Library y Web of Science, para los últimos 10 años, empleándose un total de 45 artículos como referencias bibliográficas. Desarrollo: Al Cannabis se le han atribuido efectos farmacológicos, tales como: antinociceptivo, antiepiléptico, inmunosupresivo, antiemético, estimulante del apetito, antimicrobiano, antiinflamatorio y neuroprotector. A su vez, presenta disímiles reacciones adversas como son la predisposición a varios tipos de cáncer, empeoramiento de desórdenes mentales, dificultades en el aprendizaje y el rendimiento escolar, que constituye una droga portera, entre otros. A pesar de las tendencias legalizadoras no son suficientes las razones para la legalización de esta droga, cuando su principal blanco resulta ser los adolescentes, donde los daños neurológicos que causa son irreversibles. Conclusiones: Se debe continuar explorando las potencialidades terapéuticas de los cannabinoides a partir de la elaboración de productos farmacológicos bien dosificados y controlados, pues el riesgo de sus efectos adversos es innegable y contundente(AU)

Introduction: Currently, one of the most controversial issues that greatly involves the medical field is the therapeutic use and legalization of marijuana. This millennial recognition has led to different controversies in recent decades due to the discovery of the endocannabinoid system which has revolutionized the process of research on this topic. Objective: To describe the current situation of cannabis, its therapeutic benefits and adverse effects. Material and methods: An in-depth search and review was carried out using Health Sciences descriptors in English and Spanish. A search was carried out in PubMed, SciELO, Lilacs, Cochrane Library and Web of Science databases. Publications from the last 10 years were consulted, using a total of 45 articles as bibliographic references. Development: Some pharmacological effects such as antinociceptive, antiepileptic, immunosuppressive, antiemetic, appetite stimulant, antimicrobial, anti-inflammatory and neuroprotective ones have been attributed to Cannabis. In turn, it presents dissimilar adverse reactions such as predisposition to various types of cancer, worsening of mental disorders, and difficulties with learning and school performance. Cannabis, among others, is considered a starter drug. Despite the trend towards legalization, there are not enough reasons for the legalization of this drug. Its main target turns out to be the adolescents, among which the neurological damage it causes is irreversible. Conclusions: The therapeutic potential of cannabinoids should continue to be explored from the production of well dosed and controlled pharmacological products, since the risk of their adverse effects are undeniable and overwhelming(AU)

Chemical Characteristics, Therapeutic Uses, and Legal Aspects of the Cannabinoids of Cannabis sativa: A Review

Abstract Marijuana (Cannabis sativa) is an important annual medicinal plant that belongs to the Cannabaceae family. It contains 421 substances of 18 chemical types-the most significant compound is δ-9-tetrahydrocannabinol, which causes several effects, both in the Central Nervous System and in several peripheral locations in the organism. The objectives of this scientific review are to mention the anatomical distribution, chemical characteristics and biosynthesis of cannabinoids, as well as its actions mechanisms. The endogenous cannabinoid system, the therapeutic properties of C. sativa and its action on the nociceptive control are described. Finally, the modulators of the cannabinoid system in clinical use are indicated, together with marijuana legalization benefits.

Canabinoides como uma nova opção terapêutica nas doenças de Parkinson e de Alzheimer: uma revisão de literatura / Canabinoid as a new therapeutic option in Parkinson's and Alzheimer's diseases: a literature review

Os derivados canabinoides podem ser vistos como novos potenciais terapêuticos para o tratamento da doença de Parkinson e Alzheimer. Assim, esta revisão teve como objetivo descrever os efeitos terapêuticos e adversos do uso de canabidiol e de delta-9-tetrahidrocanabinol nas doenças de Parkinson e de Alzheimer. Para tanto, foi realizada uma busca na base de dados Medline no período entre 2007 e 2017. Os descritores utilizados foram (Tetrahydrocannabinol OR Cannabidiol) AND (Parkinson OR Alzheimer) AND (Treatment OR Therapeutics). Os resultados mostraram efeitos terapêuticos promissores do canabidiol e do delta-9-tetrahidrocanabinol nestas doenças, tais como redução de sintomas motores e cognitivos, e ação neuroprotetora. Estes resultados podem ser explicados, em parte, pelos efeitos antioxidante, antiinflamatório, antagonista de receptores CB1, ou pela ativação de receptores PPAR-gama produzido por estas substâncias. Além disso, poucos efeitos adversos foram descritos, como boca seca e sonolência. Nesse contexto, estes resultados evidenciam a necessidade de novas pesquisas a respeito dos efeitos terapêuticos e adversos de canabinoides com maiores doses e períodos de exposição, para quem sabe, em um futuro próximo, ser possível olhar estas substâncias como uma opção terapêutica mais eficaz e segura para estes pacientes.

Cannabinoid derivatives can be viewed as a novel therapeutic potentials for the treatment of Parkinson's and Alzheimer's disease. Thus, this review aimed to describe the therapeutic and adverse effects of the use of cannabidiol and delta-9-tetrahydrocannabinol in Parkinson's and Alzheimer's disease. A search of the Medline database was carried out between 2007 and 2017. The descriptors used were (Tetrahydrocannabinol OR Cannabidiol) AND (Parkinson OR Alzheimer) AND (Treatment OR Therapy). The results showed promising therapeutic effects of cannabidiol and delta-9-tetrahydrocannabinol in Parkinson and Alzheimer's diseases, such as the reduction of motor and cognitive symptoms and neuroprotective action. These results may be explained, in part, by the anti-inflammatory and antioxidant effects, by CB1 receptor antagonism, or by the activation of PPAR-gamma receptors, produced by these substances. In addition, few adverse effects have been reported, such as dry mouth and drowsiness. In this context, these results highlight the need for further research on the therapeutic and adverse effects of cannabinoids with higher doses and periods of exposure, for whom, in the near future, it is possible to view these substances as a more effective and safe therapeutic option for these patients.

Therapeutic applications based on cannabinoids action / Aplicaciones terapéuticas por acción de los cannabinoides

The interest on cannabinoids became evident between the 1940 and 1950 decades. Although the active substance of the plant was not known, a series of compounds with cannabinomimetic activity were synthesized, which were investigated in animals and clinically. The most widely tested was Δ6α, 10α-THC hexyl. Δ6α, 10α-THC dimethylheptyl (DMHP) antiepileptic effects were studied in several children, with positive results being obtained in some cases. DMHP differs from sinhexyl in that its side chain is DMHP instead of n-hexyl. The first cannabinoid isolated from Cannabis sativa was cannabinol, although its structure was correctly characterized several years later. Cannabidiol was isolated some years later and was subsequently characterized by Mechoulam and Shvo. In 2013, the National Academy of Medicine and the Faculty of Medicine of the National Autonomous University of Mexico, through the Seminar of Studies on Entirety, decided to carry out a systematic review on a subject that is both complex and controversial: the relationship between marijuana and health. In recent years, studies have been conducted with cannabis in several diseases: controlled clinical trials on spasticity in multiple sclerosis and spinal cord injury, chronic, essentially neuropathic, pain, movement disorders (Gilles de Latourette, dystonia, levodopa dyskinesia), asthma and glaucoma, as well as non-controlled clinical trials on Alzheimer’s disease, neuroprotection, intractable hiccups, epilepsy, alcohol and opioid dependence and inflammatory processes.

What do Cochrane systematic reviews say about the use of cannabinoids in clinical practice?

ABSTRACT BACKGROUND: The therapeutic effects of cannabinoid compounds have been the center of many investigations. This study provides a synthesis on all Cochrane systematic reviews (SRs) that assessed the use of cannabinoids as a therapeutic approach. DESIGN AND SETTING: Review of SRs, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: A broad search was conducted in the Cochrane Database of Systematic Reviews to retrieve any Cochrane SRs that assessed the efficacy and safety of cannabinoids as a therapeutic approach. The results and key characteristics of all reviews included were summarized and discussed. RESULTS: Eight SRs were included. They assessed the use of cannabinoids for the following types of conditions: neurological (two SRs), psychiatric (two SRs), rheumatological (one SR), infectious (one SR) and oncological (two SRs). There was moderate-quality evidence showing that the use of cannabinoids reduced nausea and vomiting among adults, compared with placebo. Additionally, there was moderate-quality evidence showing that there was no difference between cannabinoids and prochlorperazine regarding the number of participants who reported vomiting, in this same population. CONCLUSIONS: This review identified eight Cochrane systematic reviews that provided evidence of unknown to moderate quality regarding the use of cannabinoids as a therapeutic intervention. Further studies are still imperative for solid conclusions to be reached regarding practical recommendations.

¿Constituyen los cannabinoides una alternativa terapéutica para insomnio? / Do cannabinoids constitute a therapeutic alternative for insomnia?

INTRODUCCIÓN: Se ha planteado que la estimulación del sueño con cannabinoides podría constituir una alternativa terapéutica en pacientes con insomnio. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos ocho revisiones sistemáticas que en conjunto incluyen tres estudios primarios, de los cuales dos corresponden a ensayos aleatorizados. Concluimos que no está claro si los cannabinoides tienen un efecto en la severidad del insomnio o en la calidad del sueño; que podrían no tener efecto en la conciliación del sueño, despertar del sueño ni comportamiento durante vigilia, y probablemente se asocian a efectos adversos frecuentes.

INTRODUCTION: It has been suggested that cannabinoids would constitute a therapeutic alternative for patients with insomnia. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified eight systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have an effect on insomnia severity or on sleep quality; that they might have no effect on sleep conciliation, sleep awakening or behavior during wakefulness, and are probably associated with frequent adverse effects.

¿Son los cannabinoides un tratamiento efectivo para la fibromialgia? / Are cannabinoids effective for fibromyalgia?

INTRODUCCIÓN: Se postula que los cannabinoides pudieran tener beneficios en la fibromialgia, sin embargo, su efectividad clínica sigue siendo un tema de discusión. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos quince revisiones sistemáticas que en conjunto incluyen dos ensayos aleatorizados pertinentes. Concluimos que no está claro si los cannabinoides tienen beneficios en la fibromialgia porque la certeza de la evidencia es muy baja. Por otra parte, están asociados a efectos adversos frecuentes.

INTRODUCTION: Cannabinoids have been proposed as a therapeutic alternative for fibromyalgia. However, their clinical effectiveness is a matter of debate. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified fifteen systematic reviews including two randomized trials overall. We concluded it is not clear whether cannabinoids have any benefit in fibromyalgia because the certainty of the evidence is very low. On the other hand, they are associated to frequent adverse effects.

Cannabinoides para el tratamiento del trastorno por abuso de cannabis / Cannabinoids for the treatment of cannabis abuse disorder

Resumen INTRODUCCIÓN: El cannabis se erige como la droga ilícita más consumida en el mundo. Actualmente no existen alternativas farmacológicas específicas para el tratamiento de su adicción, por lo que se ha postulado la utilidad del uso de cannabinoides como herramienta terapéutica. Ellos actuarían principalmente a través de la disminución de síntomas de abstinencia y craving (deseo o compulsión por consumir), pero su efectividad aún no está clara. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos siete revisiones sistemáticas que en conjunto incluyeron 15 estudios primarios, de los cuales cuatro corresponden a ensayos aleatorizados. Concluimos que el uso de cannabinoides podría resultar en poco o nulo aumento en la abstinencia al finalizar el tratamiento, y probablemente aumenta los efectos adversos.

Abstract INTRODUCTION: Cannabis stands as the most used illegal drug in the world. Currently there are no pharmacologic alternatives to treat its addiction, so the use of Cannabinoids has been postulated as a therapeutic tool. They would act mainly through decrease in abstinence and craving symptoms but its effectiveness remains unclear. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified seven systematic reviews including 15 studies, of which four were randomized trials. We concluded the use of cannabinoids might result in little or no increase in abstinence at the end of treatment, and it probably increases adverse effects.

Breve reseña sobre la farmacología de los cannabinoides / Brief review on the pharmacology of cannabinoids

Intensa resulta la controversia entre los que promueven el uso de los cannabinoides con fines terapéuticos y quienes consideran que es temprana aún la introducción de estos en la clínica, por sus efectos deletéreos para la salud humana en las diferentes etapas y condicionales del desarrollo biológico. Paralelamente se debate, entre las autoridades encargadas de velar por la salud de sus conciudadanos, la polémica de legalizar o no el consumo de la Cannabis sativa en cualquiera de sus formas y derivados naturales. Ambas polémicas han fundamentado el estudio de todas las formas de presentación y consumo de esta planta, así como de sus derivados sintéticos dados sus efectos sobre la salud de enfermos y sanos. En esta breve reseña se exponen aspectos relevantes de su farmacología, debido al interés y enorme caudal de información generado por un sinnúmero de investigadores dedicados al estudio de dicha planta y sus derivados

The controversy among those that promote the use of cannabinoids with therapeutic aims is intense and who consider that it is still early for their introduction in the clinic, due to their lethal effects for the human health in the different stages and conditionals of the biological development. In parallel it is debated, among the authorities in charge of looking after the health of their fellow citizens, the polemic of legalizing or not the consumption of the Cannabis sativa in any of their forms and natural derived. Both polemics have based the study of all the forms of presentation and consumption of this herb, as well as of its synthetic derived due to their effects on the health of sick and healthy people. In this brief review outstanding aspects of their pharmacology are exposed, due to the interest and enormous flow of information generated by a large number of investigators dedicated to the study of this herb and its derived elements

Cuidados de compaixão: regulação da maconha medicinal nos Estados Unidos da América / compassionate care: regulation of medical marijuana in the United States of America

Trata-se de uma revisão integrativa de vinte e seis artigos acadêmicos publicados entre 2010 e2014, em revistas indexadas e revisadas por pares, que examinaram a relação entre aprovaçãode leis de maconha medicinal nos Estados Unidos e agravos à saúde pública locais. São abordadasas motivações que levaram cientistas sociais a pesquisar as repercussões da regulaçãoda maconha medicinal para a sociedade. As buscas realizadas em cinco bases de dados possibilitarama identificação dos efeitos mais relevantes das mudanças legislativas estaduais e dareforma política federal de 2009, que impulsionou a comercialização de maconha medicinal,sobre a saúde pública. Especificamente, a revisão se concentra sobre taxas de mortalidade poroverdose de analgésico opióide, taxas de suicídio, taxas de acidente de trânsito com vítimasfatais, taxas de criminalidade, potência da maconha, desvio de maconha medicinal para adolescentes,exposições pediátricas não intencionais à maconha e prevalência de uso de maconhailegal. Admite-se que a maconha poderá ressurgir como opção terapêutica no tratamentopaliativo e complementar de um grande escopo de condições de saúde crônicas e terminais.No senso comum brasileiro, a maconha permanece vinculada ao crime, e o uso fitoterápico daerva in natura, assim como de seus extratos vegetais, carregado de estigma. Os achados destarevisão, entretanto, não sustentam os fundamentos que apoiam a validade de algumas preocupaçõespúblicas comumente relacionadas com a regulação da substância, como a exacerbaçãode crimes violentos. Na verdade, seus resultados surpreendem ao demonstrar evidências deque leis de maconha medicinal podem reduzir a violência, o suicídio, a overdose de analgésicoopióide, o uso de álcool e os danos de saúde pública a ele associados.

This is an integrative review of twenty-six academic studies published in indexed and peer-reviewedjournals, between 2010 and 2014, that examined the relations between medical marijuanalaws approval in the United States and local public health associated harms. It addressesthe motivations that led social scientists to research the impacts of medical marijuana regulationon society. The searches were carried out in five databases, allowing to identify the mostrelevant effects of state legislative changes and the 2009 federal policy reform, which boostedmedical marijuana sales, on public health. Specifically, this review focuses on opioid analgesicoverdose mortality rates, suicide rates, traffic fatality rates, crime rates, marijuana potency,medical marijuana diversion among teenagers, unintentional marijuana pediatric exposuresand prevalence of illegal marijuana use. It is assumed that marijuana may resurface as a treatmentoption in palliative and complementary care for a wide scope of chronic and terminalhealth conditions. Historically and culturally, brazilians associate marijuana as linked to crimeand therefore stigmatize it regardless of whether the substance appears as herbal or as plantextracts. However findings from this review do not support the fundamentals that reinforcethe validity of some public concerns commonly related to marijuana regulation, such as theexacerbation of violent crimes. Surprisingly, its results in fact show evidence that medicalmarijuana laws may reduce violence, suicide, opioid analgesic overdose, alcohol use and publichealth harms associated with it.

Cannabinoids in neurology – Brazilian Academy of Neurology / Canabinoides e seu uso em neurologia – Academia Brasileira de Neurologia

O uso do canabidiol em algumas condições neurológicas foi liberado pelo Conselho Regional de Medicina de São Paulo e pela Agência Nacional de Vigilância Sanitária (ANVISA). Especialistas em nome da Academia Brasileira de Neurologia prepararam uma posição crítica sobre o uso do canabidiol e outros derivados da cannabis em doenças neurológicas.

The use of cannabidiol in some neurological conditions was allowed by Conselho Regional de Medicina de São Paulo and by Agência Nacional de Vigilância Sanitária (ANVISA). Specialists on behalf of Academia Brasileira de Neurologia prepared a critical statement about use of cannabidiol and other cannabis derivatives in neurological diseases.