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

Immunochromatography screening devices for cannabinoids in oral fluid sample

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

Estudo de estabilidade de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol em amostras de urina seca em papel (dried urine spots) / Stability study of amphetamines, biotransformation products of cocaine and tetrahydrocannabinol in dried urine spots

O número de pessoas utilizando substâncias ilícitas de forma recreativa aumenta a cada ano, chamando a atenção de estudiosos de diversas áreas do conhecimento. Com isso, a demanda de exames toxicológicos exigida para trabalhadores, vítimas de crimes e esportistas também tem crescido. A amostra biológica mais utilizada para análises toxicológicas continua sendo a urina, visto que sua obtenção é menos invasiva, possibilita coletar grande volume de amostra e pode-se detectar substâncias até dias após ter ocorrido a exposição ou consumo. Entretanto, estas amostras necessitam de um grande volume físico para serem armazenadas e transportadas aos laboratórios, devendo ser mantidas em temperatura baixa e controlada para conservação. Outro ponto a se considerar é a quantidade de amostra insuficientemente coletada, ou extravasamento do conteúdo, contaminando outras amostras e muitas vezes, inviabilizando a análise. Uma alternativa recente para tais problemas é utilizar a técnica chamada de dried urine spots (DUS), onde poucos microlitros de urina são colocados em um papel absorvente e secos sob temperatura ambiente, preservando de agentes degradantes os componentes presentes na urina. Assim, o objetivo deste trabalho é avaliar a estabilidade das substâncias do presente estudo em alta temperatura, temperatura ambiente e em temperaturas de 4°C e -20°C. Para este fim, foi necessário desenvolver, validar e aplicar métodos de extração e determinação de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol carboxílico (THCCOOH) em amostras dried urine spot, utilizando cromatografia líquida acoplada à espectrometria de massas. Os picos foram identificados por UPLC-ESI-MS/MS, com tempo total de 5 mins utilizando fase A- água, formiato de amônio e 0,1% ácido fórmico, e B- metanol: acetonitrila (6:4) + 0,1% de ácido fórmico. A extração foi feita utilizando acetonitrila: metanol: acetona (1:1:1) +ácido fórmico 0,1%. Não foi possível iniciar a validação de THCCOOH, visto uma possível complexação do analito com o papel. Para as outras substâncias, o método cromatográfico desenvolvido se mostrou eficiente e seletivo, com LOD e LOQ de 10 ng/mL para todos os analitos, sendo linear até 1000 ng/mL, atendeu as especificações de precisão e exatidão e carryover. As amostras permaneceram estáveis ao longo de 32 dias nas temperaturas estudadas, demonstrando a segurança em se utilizar a técnica de DUS para armazenamento e transporte de amostras biológicas dentro da faixa de temperatura do estudo até 32 dias

The number of people using illegal substances in a recreational way increases each year, drawing the attention of scholars from different areas of knowledge. As a result, the demand for workplaces drug tests, toxicological tests for victims of crimes and dopping has also grown. The biological sample most used for toxicological tests remains urine, since obtaining it is less invasive, it is possible to collect a large volume of sample and it is possible to detect substances up to days after exposure or consumption has occurred. However, these samples require a large physical volume to be stored and transported to the laboratories, and must be kept at a low temperature for conservation. Another point to consider is the amount of sample insufficiently collected, or leakage of the content, causing contamination of other samples and often making the analysis unfeasible. A recent alternative to such problems is to use "dried urine spots" (DUS), where few microliters of urine are placed on absorbent paper and dried at room temperature, preserving the components present in the urine from degrading agents. Thus, the objective of this work is to evaluate the stability of the substances in this study at high temperature, room temperature and at temperatures of 4°C and -20°C. For this purpose, it was necessary to develop, validate and apply methods of extraction and determination of amphetamines and biotransformation products of cocaine and carboxylic tetrahydrocannabinol (THCCOOH) in dried urine spot samples, using liquid chromatography coupled to mass spectrometry (LC-MS). The peaks were identified liquid chromatography coupled to a mass spectrometer (UPLC-ESI-MS/MS), with a total time of 5 mins using phase A- water, ammonium formate and 0.1% formic acid, and B- methanol: acetonitrile (6:4) + 0.1% formic acid. Extraction was done using acetonitrile: methanol: acetone (1:1:1) + 0.1% formic acid. It was not possible to perform the validation of THCCOOH, given a possible complexation of the analyte with the paper. To the others substances, the chromatographic method developed proved to be efficient and selective, with LOD and LOQ of 10 ng/mL for all analytes, being linear up to 1000 ng/mL, meeting the specifications of precision and accuracy and carryover. The samples remained stable for 32 days at the temperatures studied, demonstrating the safety of using the DUS technique for storage and transport of biological samples until 32 days on temperature range studied

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)

Estudo de estabilidade de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol em amostras de urina seca em papel (dried urine spots) / Stability study of amphetamines, biotransformation products of cocaine and tetrahydrocannabinol in dried urine spots

O número de pessoas utilizando substâncias ilícitas de forma recreativa aumenta a cada ano, chamando a atenção de estudiosos de diversas áreas do conhecimento. Com isso, a demanda de exames toxicológicos exigida para trabalhadores, vítimas de crimes e esportistas também tem crescido. A amostra biológica mais utilizada para análises toxicológicas continua sendo a urina, visto que sua obtenção é menos invasiva, possibilita coletar grande volume de amostra e pode-se detectar substâncias até dias após ter ocorrido a exposição ou consumo. Entretanto, estas amostras necessitam de um grande volume físico para serem armazenadas e transportadas aos laboratórios, devendo ser mantidas em temperatura baixa e controlada para conservação. Outro ponto a se considerar é a quantidade de amostra insuficientemente coletada, ou extravasamento do conteúdo, contaminando outras amostras e muitas vezes, inviabilizando a análise. Uma alternativa recente para tais problemas é utilizar a técnica chamada de dried urine spots (DUS), onde poucos microlitros de urina são colocados em um papel absorvente e secos sob temperatura ambiente, preservando de agentes degradantes os componentes presentes na urina. Assim, o objetivo deste trabalho é avaliar a estabilidade das substâncias do presente estudo em alta temperatura, temperatura ambiente e em temperaturas de 4°C e -20°C. Para este fim, foi necessário desenvolver, validar e aplicar métodos de extração e determinação de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol carboxílico (THCCOOH) em amostras dried urine spot, utilizando cromatografia líquida acoplada à espectrometria de massas. Os picos foram identificados por UPLC-ESI-MS/MS, com tempo total de 5 mins utilizando fase A- água, formiato de amônio e 0,1% ácido fórmico, e B- metanol: acetonitrila (6:4) + 0,1% de ácido fórmico. A extração foi feita utilizando acetonitrila: metanol: acetona (1:1:1) +ácido fórmico 0,1%. Não foi possível iniciar a validação de THCCOOH, visto uma possível complexação do analito com o papel. Para as outras substâncias, o método cromatográfico desenvolvido se mostrou eficiente e seletivo, com LOD e LOQ de 10 ng/mL para todos os analitos, sendo linear até 1000 ng/mL, atendeu as especificações de precisão e exatidão e carryover. As amostras permaneceram estáveis ao longo de 32 dias nas temperaturas estudadas, demonstrando a segurança em se utilizar a técnica de DUS para armazenamento e transporte de amostras biológicas dentro da faixa de temperatura do estudo até 32 dias

The number of people using illegal substances in a recreational way increases each year, drawing the attention of scholars from different areas of knowledge. As a result, the demand for workplaces drug tests, toxicological tests for victims of crimes and dopping has also grown. The biological sample most used for toxicological tests remains urine, since obtaining it is less invasive, it is possible to collect a large volume of sample and it is possible to detect substances up to days after exposure or consumption has occurred. However, these samples require a large physical volume to be stored and transported to the laboratories, and must be kept at a low temperature for conservation. Another point to consider is the amount of sample insufficiently collected, or leakage of the content, causing contamination of other samples and often making the analysis unfeasible. A recent alternative to such problems is to use "dried urine spots" (DUS), where few microliters of urine are placed on absorbent paper and dried at room temperature, preserving the components present in the urine from degrading agents. Thus, the objective of this work is to evaluate the stability of the substances in this study at high temperature, room temperature and at temperatures of 4°C and -20°C. For this purpose, it was necessary to develop, validate and apply methods of extraction and determination of amphetamines and biotransformation products of cocaine and carboxylic tetrahydrocannabinol (THCCOOH) in dried urine spot samples, using liquid chromatography coupled to mass spectrometry (LC-MS). The peaks were identified liquid chromatography coupled to a mass spectrometer (UPLC-ESI-MS/MS), with a total time of 5 mins using phase A- water, ammonium formate and 0.1% formic acid, and B- methanol: acetonitrile (6:4) + 0.1% formic acid. Extraction was done using acetonitrile: methanol: acetone (1:1:1) + 0.1% formic acid. It was not possible to perform the validation of THCCOOH, given a possible complexation of the analyte with the paper. To the others substances, the chromatographic method developed proved to be efficient and selective, with LOD and LOQ of 10 ng/mL for all analytes, being linear up to 1000 ng/mL, meeting the specifications of precision and accuracy and carryover. The samples remained stable for 32 days at the temperatures studied, demonstrating the safety of using the DUS technique for storage and transport of biological samples until 32 days on temperature range studied

Efficacy of cannabinoids in fibromyalgia: a literature review / Eficacia de los cannabinoides en la fibromialgia: revisión de la literatura

Abstract Fibromyalgia is a chronic disease of unclear etiology, involving a neural oversensitization and impaired pain modulation, in addition to a clinical deficiency of the endocannabinoid system. Fibromyalgia is associated with a number of somatic and psychological disorders and hence multiple pharmacological approaches have been used, including opioids, antidepressants, antiepileptics, and more recently medical cannabis. This narrative review comprises a review of the current literature on the efficacy of cannabinoids in fibromyalgia. The studies describe a possible influence of cannabis on pain control in patients with fibromyalgia, with positive effects on quality of life and sleep. The use of cannabis seems to be beneficial in patients with fibromyalgia; however, more robust studies are still needed to establish is actual efficacy in pain management, quality of life and improvement of associated symptoms.

Resumen La fibromialgia es una enfermedad crónica, cuya etiología no es clara, en la que se involucra una sobresensibilización neural y disminución de la modulación del dolor, así como una deficiencia clínica del sistema endocannabinoide. Está asociada a una variedad de trastornos somáticos y psicológicos, por lo cual se han utilizado múltiples abordajes farmacológicos, entre ellos opioides, antidepresivos, antiepilépticos y, recientemente, cannabis medicinal. En esta revisión narrativa se hace una reseña de la literatura actual relacionada con la eficacia de los cannabinoides en la fibromialgia. Los estudios describen una posible influencia del cannabis sobre el control del dolor en pacientes con fibromialgia, con efectos positivos sobre la calidad de vida y el sueño. El uso del cannabis parece tener beneficios en los pacientes con fibromialgia; sin embargo, aún se requieren estudios más robustos para establecer su verdadera eficacia en el manejo del dolor, calidad de vida y mejoría de los síntomas asociados.

Disforia de género en el adulto con enfermedad coronaria. Reporte de caso y revisión de la literatura / Adult Gender Dysphoria with Coronary Disease. Case Report and Literature Review

RESUMEN Introducción: La disforia de género (DG) hace referencia a una marcada incongruencia entre la identidad de género y el sexo biológico, que genera un malestar clínico de al menos 6 meses de duración. Métodos: Reporte de caso y revisión no sistemática de la literatura. Presentación del caso: Mujer transgénero de 56 años, con historia de enfermedad coronaria y un segundo evento tromboembólico posterior a la automedicación de terapia hormonal. Después del tratamiento agudo de su afección cardiovascular, solicitó tratamiento para su DG. Discusión: La DG requiere un tratamiento multidisciplinario. La THC es el pilar del tratamiento. Se ha documentado que el uso de presentaciones orales de estrógenos puede aumentar el riesgo de eventos tromboembólicos en pacientes mayores de 40 años, principalmente cuando tienen factores de riesgo cardiovascular. Conclusiones: Se debe ofrecer un tratamiento integral a todas las personas con DG para aliviar el malestar psicológico, disminuir la comorbilidad psiquiátrica y mejorar su calidad de vida. Hasta el momento hay poca evidencia científica respecto a la THC en mujeres transgénero mayores de 40años, por lo que se recomienda una vigilancia multidisciplinaria, estrecha y rigurosa, en especial cuando hay riesgo cardiovascular.

ABSTRACT Introduction: Gender dysphoria (GD) refers to a marked incongruity between gender identity and biological sex. GD generates a significant clinical discomfort for at least six months. Methods: Case report and non-systematic literature review. Case presentation: A 56-year-old male-to-female patient, who had a history of coronary disease and a second thromboembolic event after hormone therapy (self-medicated). Once she had received acute management for the cardiovascular disease, she consulted for her GD. Discussion: GD requires multidisciplinary management. Cross-sex hormonal therapy is considered the main treatment. It has been documented that oral oestrogen preparations may increase the risk of thromboembolic events in patients over the age of 40, especially when they have cardiovascular risk factors. Conclusions: Comprehensive treatment should be offered to everyone who has GD, to relieve psychological distress, decrease psychiatric comorbidity and improve quality of life. To date, there is little scientific evidence regarding cross-sex hormonal therapy in transgender women over the age of 40; we therefore recommend multidisciplinary, close and rigorous monitoring, in particular when they have cardiovascular risk.

Daño pulmonar asociado al uso de cigarrillos electrónicos-vapeadores / Pulmonary damage associated with the use of electronic cigarettes or vapers

Ha habido mucha discusión sobre los efectos dañinos para la salud producidos por los cigarrillos electrónicos o vapeadores y su utilidad como ayuda para dejar de fumar. Cada vez aparecen más publicaciones con efectos deletéreos sobre la salud. Esta discusión se ha acentuado en los últimos años, por el importante aumento del uso de los vapeadores en todo el mundo, especialmente entre los adolescentes y adultos jóvenes. En septiembre de 2019 el Centro de Control y Prevención de Enfermedades (CDC) de los EE. UU. alertó sobre un importante número de casos de enfermedad pulmonar asociada al uso de cigarrillo electrónico (EVALI: e-cigarette or vaping associated lung injury). Epidemiológicamente se consideró un brote que al 17 de enero, 2020 ha presentado 2.668 pacientes hospitalizados, con 57 fallecidos. Durante la semana del 15 de septiembre 2019 ocurrió el 'peak' de hospitalizaciones por EVALI. La mayoría eran varones jóvenes. El 82% usó productos con Tetrahidrocanabinoides (THC) y el 14% productos con nicotina. En el lavado bronquio-alveolar de 51 casos de EVALI se encontró la presencia de acetato de Vitamina E, producto utilizado como espesante para la elaboración de productos de 'vapeo' que contienen THC, lo que lo hace un posible factor causal, pero no se puede descartar el papel de otros compuestos tóxicos. Las principales sociedades científicas del mundo y la OMS han advertido de los riesgos a largo plazo del uso de los cigarrillos electrónicos y recomiendan su control y regulación.

There has been a lot of discussion about the harmful health effects caused by electronic cigarettes or vapers and their usefulness as a smoking cessation aid. More and more publications appear with deleterious effects on health. This discussion has been straightened in recent years, due to the significant increase in the use of vapers worldwide, especially among adolescents and young adults. In September 2019, the US Center for Disease Control and Prevention warned of a significant number of cases of lung disease associated with the use of electronic cigarettes (EVALI: e-cigarette or vaping associated lung injury). Epidemiologically it was considered an outbreak that as of January 17, 2020 presented 2668 hospitalized patients, with 57 deaths. During the week of September 15, 2019 the peak of hospitalizations for EVALI occurred. The majority were young men. 82% of them used products with Tetrahydrocanabinoids (THC) and 14% products with nicotine. In the bronchoalveolar lavage of 51 cases of EVALI, the presence of Vitamin E acetate was found, a product used as a thickener for the elaboration of vaping products containing THC, which makes it a possible causal factor, but it cannot be ruled out the contribution of other toxic compounds. The world's leading scientific societies and World Health Organization have warned of the long-term risks of using electronic cigarettes and recommend their control and regulation.

Marihuana en México, ¿droga recreativa o medicina? / Marijuana in Mexico, recreational drug or medicine?

El tema que discutimos tiene una relevancia que alcanza todos los ámbitos de la sociedad actual, debido a que incluye factores sociales, políticos, económicos y de salud; sin embargo, es de mencionar la situación risible que ocurre en relación con el consumo de marihuana en México, dado que los artículos 477 y 479 de la Ley General de Salud determinan su posible portación y consumo personal a la cantidad de 5 g del estupefaciente. Dicho en otras palabras, el uso con fines médicos se encuentra aún penalizado e inclusive mal visto dentro de la práctica, mientras que la finalidad recreativa sobre la posesión y el uso tanto de la marihuana como de algún derivado del tetrahidrocannabinol (THC) son contemplados dentro de la ley explícitamente. Esto ha quedado ejemplificado claramente el pasado 24 de noviembre de 2015, fecha en la cual, a pesar de la ley ya existente, el Pleno de la Suprema Corte de Justicia de la Nación concedió a cuatro personas el derecho a la «... producción, uso y autoconsumo del estupefaciente cannabis y el psicotrópico "THC" para fines "lúdicos"¼; al compararlo con los casos actuales que han obtenido la autorización pertinente del gobierno para el uso médico, son muchos menos. Si bien el 19 de junio de 2017 se aprobó el uso medicinal de la marihuana en productos con un contenido neto de THC < 1%, la Cofepris (Comisión Federal para la Protección contra Riesgos Sanitarios) dio a conocer los reglamentos en materia de control sanitario del cannabis y sus derivados hasta finales de 2018; tal hecho, dejó a merced de la obtención de un permiso para la importación de medicamentos a base del psicoactivo provenientes del extranjero acorde a lo escrito en el artículo 290. Asimismo destaca que los permisos solo pueden ser otorgados tras la ordenanza de un juez, situación que hasta la fecha continúa como «difícil¼, ya que tras recibir aproximadamente 534 solicitudes, solo 9 se habían autorizado a 5 de septiembre de 2018, esto según el portal del propio gobierno de México.

The issue we are discussing is relevant to all areas of today's society, as it includes social, political, economic and health factors; however, it is worth mentioning the laughable situation that occurs in relation to the consumption of marijuana in Mexico, given that articles 477 and 479 of the General Health Law determine its possible possession and personal consumption to the amount of 5 g of the drug. In other words, use for medical purposes is still criminalised and even frowned upon in practice, while the recreational purpose of possession and use of both marijuana and a derivative of tetrahydrocannabinol (THC) is explicitly contemplated in the law.This was clearly exemplified on 24 November 2015, when, despite the existing law, the Plenary of the Supreme Court of Justice of the Nation granted four people the right to "... production, use and self-consumption of the narcotic drug cannabis and the psychotropic "THC" for "recreational" purposes"; when compared to the current cases that have obtained the relevant government authorisation for medical use, there are far fewer. Although the medical use of marijuana in products with a net THC content < 1% was approved on 19 June 2017, the Cofepris (Comisión Federal para la Protección contra Riesgos Sanitarios) released the regulations on the sanitary control of cannabis and its derivatives until the end of 2018; this fact left the importation of medicines based on the psychoactive drug from abroad subject to obtaining a permit in accordance with the provisions of article 290. It also points out that permits can only be granted following a judge's order, a situation that to date continues to be "difficult", as after receiving approximately 534 applications, only 9 had been authorised as of 5 September 2018, according to the Mexican government's own website.

Cannabis medicinal: riesgos relacionados con la indicación previa a su aprobación / Medical cannabis: Risks related to its indication prior to approval

En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.

In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.

Cannabis and the exocannabinoid and endocannabinoid systems. Their use and controversies

Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.

Medición de drogas ilícitas en aguas residuales: estudio piloto en México / Assessing illicit drugs in wastewater: a pilot study in Mexico

Resumen: Objetivo: Monitorear el consumo de drogas a través de la medición de sus metabolitos en aguas residuales. Material y métodos: Se obtuvieron muestras de 31 plantas de tratamiento de agua residual y de 95 sitios con poblaciones específicas (38 escuelas, 42 unidades de tratamiento de adicciones y 15 centros de readaptación social). Usando cromatografía líquida de ultra-alta resolución, se midieron nueve metabolitos de seis drogas. Resultados: Ocho de nueve metabolitos de drogas fueron identificados en aguas residuales. Los metabolitos de marihuana (THC-COOH), cocaína (benzoilecgonina) y metanfetamina fueron identificados en escuelas, centros de readaptación social y de tratamiento de adicciones. En Nuevo Laredo, Culiacán y Torreón se encontraron los consumos per cápita más elevados de cocaína, marihuana, anfetamina y metanfetamina. Conclusiones: El monitoreo del uso de drogas a través de aguas residuales es factible en México y podría constituir un sistema de vigilancia para identificar cambios de su consumo en el tiempo.

Abstract: Objective: Monitor drug use through wastewater metabolite measurement. Materials and methods: Wastewater samples were obtained from 31 wastewater treatment plants and 95 sites with specific populations (38 schools, 42 units of addiction treatment and 15 penitentiaries). Using ultra high liquid chromatography, we measured nine metabolites from six drugs. Results: Eight out of nine drug metabolites were identified in the samples. Marijuana (THC-COOH), cocaine (benzoylecgonine) and methamphetamine were identified in schools, centers of addiction treatment and penitentiaries. Nuevo Laredo, Culiacan and Torreon had the highest consumption of cocaine, marijuana, amphetamine and methamphetamine. Conclusions: Monitoring drug use through wastewater is feasible in Mexico and could constitute a surveillance system to identify changes in the time.

Cannabis medicinal en Argentina: perspectiva desde la salud pública / Medicinal cannabis in Argentina: a public health perspective

Esta revisión analiza la situación actual de la utilización del como herramienta terapéutica dentro del ámbito de la salud en Argentina, haciendo referencia a los distintos actores involucrados y dilemas futuros que pueden presentarse. Paracomprender en su totalidad el marco social, cultural e histórico, se desarrollan distintos aspectos, como la descripción química y biológica del , evolución del consumo a través de la historia, las repercusiones del consumo y las distintas aplicaciones que tiene en el campo de la medicina. También se describen las diferentes realidades que hay en el mundo, así como las legislaciones de otros países y la comparación de estas con la que tenemos en nuestro país. Finalmente se mencionan los desafíos pendientes y sus posibles abordajes.(AU)

This review analyzes the current situation of the use of cannabis as a therapeutic tool in the field of health in Argentina,referring to the different actors involved and future dilemmas that may arise. To fully understand the social, cultural andhistorical framework, different aspects can be defined, such as the chemical and biological description of cannabis, theevolution of consumption throughout history, the repercussions of recreational consumption and the different applicationsthat it has on the medical field. It also describes the different realities that exist in the world, as well as the laws of othercountries and the comparison of these with the one we have in our country. Finally, the pending challenges and theirpossible approaches, are mentioned.(AU)

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

Avaliação da presença de cocaína e anfetamina em amostras de sangue post mortem e de indivíduos vivos, utilizando técnica de microextração em fase líquida (HF-LPME) / Amphetamine, cocaine and tetrahydrocannabinol evaluation in blood samples of living people and post mortem blood samples using microextraction technique in liquid phase (HF-LPME)

Estima-se atualmente que mais de 5% da população mundial vem fazendo uso recreativo de algum tipo de substância psicoativa, sendo que o direito a esse uso é tema recorrente da sociedade contemporânea. Por apresentar riscos associados à saúde e a segurança das populações, o uso abusivo dessas substâncias tem instigado a toxicologia social na busca de respostas, com as quais se possa caracterizar, analisar e gerenciar esses riscos. Drogas de grande consumo no Brasil são a anfetamina, cocaína e Cannabis sativa. Esta tese desenvolveu uma nova metodologia para detectar e quantificar anfetamina, cocaína e tetrahidrocanabinol em sangue total, com uso de microextração em fase líquida via fibra de polipropileno (HF-LPME), seguida de cromatografia gasosa acoplada a espectrometria de massa (GC-MS). Trata-se de uma técnica que apresenta vantagens sobre as tradicionais, uma vez que demanda quantidades menores de solvente orgânico, diminuindo riscos e custos de processo. Também propôs um estudo com a aplicação dos métodos em 69 amostras de sangue de vivos e de post mortem, as quais foram obtidas por convênio com a superintendência da polícia técnica científica de São Paulo (SPTC/SP). Os métodos desenvolvidos foram validados de acordo com diretrizes internacionais de interesse forense. Como resultado da validação, os métodos desenvolvidos se mostraram precisos e exatos para anfetamina e cocaína. O limite de detecção da cocaína foi de 5 ng . mL-1 e o limite de quantificação de 10 ng . mL-1. Quanto a anfetamina, os limites de detecção e de quantificação foram de 5 ng . mL-1. A técnica de HF-LPME não foi aplicável ao tetraidrocanabinol (Δ9-THC). Como resultado da análise das amostras, 40% delas apresentaram resultados positivos para cocaína. Desses positivos, 35% foram oriundos das matrizes de sangue de vivos e 64% oriundos de sangue post mortem. Nenhuma delas apresentou resultado quantificável para anfetamina

It is currently estimated that more than 5% of the world's population has been doing recreational use of some kind of psychoactive substances and the legal right to such use is a recurring theme debated by contemporary society. Due to the risks associated with populations health and safety, the abusive use of these substances has been instigating by social toxicology to search for answers to characterize, analyze and manage these risks. Drugs of great consumption in Brazil are, amphetamine cocaine and marijuana. This thesis proposes to develop a new methodology to detect and quantify psychoactive drugs in whole blood with the use of liquid phase microextraction by polypropylene fiber (HFLPME), followed by gas chromatography coupled to mass spectrometry (GC-MS). It is a technique that presents advantages compared with traditional ones, because of the smaller amounts demands of organic solvent, reducing risks and process costs. It also proposes a study with 69 blood samples taken from living persons and post mortem blood samples, which were obtained by agreement with the Superintendency of São Paulo Scientific Technical Police (SPTC / SP). The methods developed were validated according to international guidelines of forensic interest. As a result of the validation, the methods developed were precise and accurate for amphetamine and cocaine. The limit of cocaine detection was 5 ng . mL-1 and the limit of quantification was 10 ng . mL-1. As for amphetamine, the limits of detection and quantification were 5 ng . mL-1. The HF-LPME technique was not applicable to tetrahydrocannabinol (Δ9-THC). As a result of the sample analysis, 40% of them presented positive results for cocaine. Of these, 35% were from blood samples taken from living persons and 64% from the post mortem blood samples. None of the samples presented quantifiable results for amphetamine

Los pro y contra de la legalización de la marihuana / Pros and cons of legalizing marijuana

Ya son varios los países que han aceptado la marihuana como una droga "blanda", diferente a otras más peligrosas. Incluso se le ha atribuido diversas propiedades terapéuticas. Otros sin embargo piensan que su uso debería prohibirse, dadas las interferencias mentales y las alteraciones del comportamiento que produce, ya sea por su consumo esporádico, como también por los daños permanentes a que lleva su consumo crónico. Con el objeto de aclarar estas divergentes apreciaciones, se revisa la literatura científica existente. De ello se deduce el grave riesgo de su consumo crónico, especialmente para el adolescente por el significativo incremento de cuadros psicóticos y esquizofrénicos, los cuales pueden llegar a ser permanentes, mientras que su consumo durante el embarazo daña el desarrollo cerebral del feto en forma similar a lo que hace el alcohol en el síndrome fetal alcohólico. Investigaciones científicas también señalan que al fumar sus hojas, se va produciendo un daño bronquial, aún más grave que con el tabaco, incluyendo el cáncer pulmonar. En conclusión, el concepto de que la marihuana es una droga "blanda", libre de riesgos para la salud, constituye un grave error, dado la concluyente investigación científica disponible que señala lo contrario.

There are already several countries that have accepted marijuana as a soft drug, separating it from more dangerous ones. Yarious therapeutic properties have even been attributed to its use. Others, however, think that its use should be prohibited due to the mental interference and behavioral changes produced either by its occasional use as well as the permanent mental damage linked to chronic marijuana use. In order to clarify this divergence of opinions, the scientific literature is reviewed. It is concluded that there is a serious risk, especially for teenagers, associated to chronic marijuana use due to the presence of more frequent psychotic and schizophrenic episodes, which can be permanent, while consumption during pregnancy results in brain damage to the fetus, similar to fetal alcohol syndrome. Scientific research also indicated that smoking marijuana produces an even more severe bronchial damage than tobacco, with risk of lung cancer. In conclusion, the notion that marijuana is a risk-free soft drug is a serious mistake, based on the available conclusive scientific research that shows the opposite.

A neurotoxicidade da Cannabis sativa e suas repercussões sobre a morfologia do tecido cerebral / Cannabis sativa neurotoxicity and impacts on the brain tissue morphology

Para a compreensão das repercussões psicológicas e comportamentais verificadas em usuários de Cannabis sativa, experimentos têm sido desenvolvidos analisando a relação entre a intensidade do uso da droga e biomarcadores de lesão e inflamação. Dessa forma, este estudo teve como objetivo realizar pesquisa bibliográfica, relacionando marcadores bioquímicos de neurotoxicidade e suas repercussões sobre a morfologia do tecido cerebral em usuários de Cannabis sativa, durante a exposição ao Δ9-THC por via intravenosa e em pesquisas in vitro. Trata-se de uma revisão narrativa cuja pesquisa bibliográfica foi realizada nos bancos de dados PubMed, SciELO e Google Acadêmico, utilizando-se como critério de inclusão os seguintes termos: "Cannabis Sativa", "marijuana", "maconha", "Δ9-THC", "neurotrophins", "neurotrofinas", "prostaglandins", "prostaglandinas", "BDNF" e "NGF". Dessa forma, foram selecionados 40 artigos para integrar a presente revisão, datados de 1987 a 2013. O período de realização da pesquisa bibliográfica foi de agosto de 2011 a maio de 2013. Foi possível identificar os tipos e a magnitude das alterações morfológicas e bioquímicas decorrentes do uso de Cannabis sativa ou da exposição ao Δ9-THC. De uma forma geral, foi constatada a diminuição das massas cinzenta e branca do cérebro, da densidade do hipocampo, do volume das células neurais, entre outros. Foram constatadas também alterações nos níveis séricos de neurotrofinas e na biossíntese de prostaglandinas, de acordo com a metodologia utilizada ou região avaliada. Esses achados poderiam estar relacionados às mudanças comportamentais observadas em usuários de Cannabis sativa, esclarecendo, por exemplo, diversos sintomas psíquicos relatados na literatura.

In order to understand psychological and behavioral impact among Cannabis sativa users, experiments have been developed by analyzing the relationship between the intensity of the use with injury and inflammation biomarkers. Therefore, this paper aimed to carry out a literature review, relating biochemical markers of neurotoxicity and their impact on morphology of brain tissue in Cannabis sativa users, during the exposure to Δ9-THC intravenously and in in vitro studies. This is a narrative review whose bibliographic research was managed in PubMed, SciELO and Google Scholar databases, using the following terms as inclusion criterion: "Cannabis sativa", "marijuana", "maconha", "Δ9-THC", "neurotrophins", "neurotrofinas", "prostaglandins", "prostaglandinas", "BDNF" and "NGF". Thereby, 40 articles were selected to integrate the present review, dated from 1987 to 2013. The period of this literature review was from August 2011 to May 2013. It was possible to identify the types and the magnitude of morphological and biochemical changes resulting from the Cannabis sativa use or exposure to Δ9-THC. In general, a reduction was found in gray and white brain mass, in density of hippocampus, in the volume of nerve cells, among others. We also observed changes in serum levels of neurotrophins and in prostaglandin biosynthesis, in accordance with methodology used or the evaluated area. These findings could be related to behavioral changes observed in Cannabis sativa users, clarifying, for instance, many psychological symptoms reported in literature.