Adult Medical Cannabinoid Use and Changes in Prescription Controlled Substance Use.

Introduction: Nonopioid-based strategies for managing chronic noncancer pain are needed to help reduce overdose deaths. Although lab studies and population-level data suggest that cannabinoids could provide opioid-sparing effects, among medical cannabis participants they may also impact overdose risk by modifying other controlled substance use such as sedative hypnotics. However, no study has combined observational data at the individual level to empirically address interactions between the use of cannabinoids and prescribed controlled substances. Methods: Electronic health records, including prescription drug monitoring program data, from a large multisite medical cannabis program in New York State were abstracted for all participants with noncancer pain and recently prescribed noncannabinoid controlled substances who completed a new intake visit from April 15, 2018-April 14, 2019 and who remained actively in treatment for >180 days. Participants were partitioned into two samples: those with recent opioid use and those with active opioid use and co-use of sedative hypnotics. A patient-month level analysis assessed total average equivalent milligrams by class of drug (i.e., cannabinoid distinguishing tetrahydrocannabinol [THC] vs. cannabidiol [CBD], opioids, and sedative-hypnotics) received as a time-varying outcome measure across each 30-day "month" period postintake for at least 6 months for all participants. Results: Sample 1 of 285 opioid users were 61.1 years of age (±13.5), 57.5% female, and using an average of 49.7 (±98.5) morphine equivalents daily at intake. Unadjusted analyses found a modest decline in morphine equivalents to 43.9 mg (±94.1 mg) from 49.7 (±98.5) in month 1 (p=0.047) while receiving relatively low doses of THC (2.93 mg/day) and CBD (2.15 mg/day). Sample 2 of 95 opioid and sedative-hypnotic users were 60.9 years of age (±13.1), 63.2% female, and using an average of 86.6 (±136.2) morphine equivalents daily, and an average of 4.3 (±5.6) lorazepam equivalents. Unadjusted analyses did not find significant changes in either morphine equivalents (p=0.81) or lorazepam equivalents (p=0.980), and patients similarly received relatively low doses of THC (2.32 mg/day) and CBD (2.24 mg/day). Conclusions: Findings demonstrated minimal to no change in either opioids or sedative hypnotics over the 6 months of medical cannabis use but may be limited by low retention rates, external generalizability, and an inability to account for nonprescribed substance use.

Knowledge, attitudes, and prescribing patterns of cannabis and cannabinoid-containing medicines among European healthcare workers: a systematic literature review.

BACKGROUND: Since the introduction of the National Medical Cannabis Programme in The Netherlands, many other countries in Europe have made medical cannabis (MC) and cannabis-based medicines (CBMs) available. However, each of them has implemented a unique legal framework and reimbursement strategy for these products. Therefore, it is vital to study healthcare professionals' knowledge level (HCP) and HCPs in-training regarding both medical uses and indications and understand their safety concerns and potential barriers for MC use in clinical practice. METHODS: A comprehensive, systematic literature review was performed using PubMed/MEDLINE, EMBASE, and Google Scholar databases, as well as PsychINFO. Grey literature was also included. Due to the high diversity in the questionnaires used in the studies, a narrative synthesis was performed. RESULTS: From 6995 studies retrieved, ten studies, all of them being quantitative survey-based studies, were included in the review. In most studies, the majority of participants were in favor of MC and CBMs use for medical reasons. Other common findings were: the necessity to provide additional training regarding medical applications of cannabinoids, lack of awareness about the legal status of and regulations regarding MC among both certified physicians, as well as prospective doctors and students of other medicals sciences (e.g., nursing, pharmacy). CONCLUSIONS: For most European countries, we could not identify any studies evaluating HCPs' knowledge and attitudes towards medicinal cannabis. Therefore, similar investigations are highly encouraged. Available evidence demonstrates a need to provide medical training to the HCPs in Europe regarding medical applications of cannabinoids.

Possible treatment and strategies for COVID-19: review and assessment.

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.

Medical cannabis in the UK: From principle to practice.

BACKGROUND: In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems. AIMS: Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes. OUTCOMES: Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions. CONCLUSIONS: There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.

Economic Evaluation of Cannabinoid Oil for Dravet Syndrome: A Cost-Utility Analysis.

INTRODUCTION: Cannabinoid oils are being increasingly used to treat Dravet syndrome, yet the long-term costs and outcomes of this approach are unknown. Thus, we examined the cost effectiveness of cannabinoid oil as an adjunctive treatment (added to clobazam and valproate), compared with adjunctive stiripentol or with clobazam and valproate alone, for the treatment of Dravet syndrome in children. METHODS: We performed a probabilistic cost-utility analysis from the perspective of the Canadian public health care system, comparing cannabinoid oil and stiripentol (both on a background of clobazam and valproate) with clobazam and valproate alone. Costs and quality-adjusted life-years (QALYs) were estimated using a Markov model that followed a cohort of children aged from 5 to 18 years through model states related to seizure frequency. Model inputs were obtained from the literature. The cost effectiveness of adjunctive cannabinoid oil, adjunctive stiripentol, and clobazam/valproate alone was assessed through sequential analysis. The influence of perspective and other assumptions were explored in scenario analyses. All costs are expressed in 2019 Canadian dollars, and costs and QALYs were discounted at a rate of 1.5% per year. RESULTS: The incremental cost per QALY gained with the use of adjunctive cannabinoid oil, from the health care system perspective, was $32,399 compared with clobazam and valproate. Stiripentol was dominated by cannabinoid oil, producing fewer QALYs at higher costs. At a willingness-to-pay threshold of $50,000, cannabinoid oil was the optimal treatment in 76% of replications. From a societal perspective, cannabinoid oil dominated stiripentol and clobazam/valproate. The interpretation of the results was insensitive to model and input assumptions. CONCLUSION: Compared with clobazam/valproate, adjunctive cannabinoid oil may be a cost-effective treatment for Dravet syndrome, if a decision maker is willing to pay at least $32,399 for each QALY gained. The opportunity costs of continuing to fund stiripentol, but not cannabinoid oil, should be considered.

Evolution of Italian laws banning trafficking, use and abuse of psychotropic drugs.

The penalty system implemented by Italian law still represents a barrier against psychoactive drugs and drug addiction, especially at a time when the age of first consumption has considerably dropped. Presidential Decree n. 309 of October 9, 1990 entitled "Consolidation of the laws governing drugs and psychotropic substances, the prevention, treatment and rehabilitation of drug addicts", and referred to as Presidential Decree 309/90, is the reference text for the cultivation, production, trade and use of narcotics and other psychoactive substances in Italy. The Presidential Decree has its origins in the now-forgotten law of December 22, 1975, n. 685, amended by law 162/90, which provided a draft of the current Presidential Decree 309/90. The current text has been amended numerous times over the years.

Cannabis and Cannabinoids in Mood and Anxiety Disorders: Impact on Illness Onset and Course, and Assessment of Therapeutic Potential.

BACKGROUND AND OBJECTIVES: Cannabis use is common in people with and mood and anxiety disorders (ADs), and rates of problematic use are higher than in the general population. Given recent policy changes in favor of cannabis legalization, it is important to understand how cannabis and cannabinoids may impact people with these disorders. We aimed to assess the effects of cannabis on the onset and course of depression, bipolar disorder, ADs, and post-traumatic stress disorder (PTSD), and also to explore the therapeutic potential of cannabis and cannabinoids for these disorders. METHODS: A systematic review of the literature was completed. The PubMed® database from January 1990 to May 2018 was searched. We included longitudinal cohort studies, and also all studies using cannabis or a cannabinoid as an active intervention, regardless of the study design. RESULTS: Forty-seven studies were included: 32 reported on illness onset, nine on illness course, and six on cannabinoid therapeutics. Cohort studies varied significantly in design and quality. The literature suggests that cannabis use is linked to the onset and poorer clinical course in bipolar disorder and PTSD, but this finding is not as clear in depression and anxiety disorders (ADs). There have been few high-quality studies of cannabinoid pharmaceuticals in clinical settings. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These conclusions are limited by a lack of well-controlled longitudinal studies. We suggest that future research be directed toward high-quality, prospective studies of cannabis in clinical populations with mood and ADs, in addition to controlled studies of cannabinoid constituents and pharmaceuticals in these populations. (Am J Addict 2019;00:00-00).

Cost-effectiveness of cannabinoids for pediatric drug-resistant epilepsy: protocol for a systematic review of economic evaluations.

BACKGROUND: Drug-resistant epilepsy negatively impacts the quality of life and is associated with increased morbidity and mortality and high costs to the healthcare system. Cannabis-based treatments may be effective in reducing seizures in this population, but whether they are cost-effective is unclear. In this systematic review, we will search for cost-effectiveness analyses involving the treatment of pediatric drug-resistant epilepsy with cannabis-based products to inform decision-making by public healthcare payers about reimbursement of such products. We will also search for cost-effectiveness analyses of other pharmacologic treatments for pediatric drug-resistant epilepsy, as well as estimates of healthcare resource use, costs, and utilities, for use in a subsequent cost-utility analysis to address this decision problem. METHODS: We will search the published and gray literature for economic evaluations of cannabis-based products and other pharmacologic treatments for pediatric drug-resistant epilepsy, as well as resource utilization and utility studies. Two independent reviewers will screen the title and abstract of each identified record and the full-text version of any study deemed potentially relevant. Study and population characteristics, the incremental cost-effectiveness ratio (ICER), as well as total costs and benefits, will be extracted, and quality will be assessed by use of the Drummond and CHEERS checklists; context-specific issues will also be considered. From model-based cost-utility and cost-effectiveness analyses, we will extract and summarize the model structure, including health states, time horizon, and cycle length. From resource utilization studies, we will extract data about the frequency of resource use (e.g., neurology visits, emergency department visits, admissions to hospital). From utility studies, we will extract the utility for each health state, the source of the preferences (e.g., child, parent, patient, general public), and the method of elicitation. DISCUSSION: Drug-resistant epilepsy in children is associated with important costs to the healthcare system, and decision-makers require high-quality evidence on which to base reimbursement decisions. The results of this review will be useful to both decision-makers considering the decision problem of whether to reimburse cannabis-based products through public formularies and to analysts conducting studies in this area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no.: CRD42018099591 .

[A brief history of marijuana in the western world]. / Breve historia sobre la marihuana en Occidente.

Marijuana is a substance with a long and controversial history. At different times in its history, which goes back over 5,000 years, this plant has been used for different purposes, ranging from recreational and leisure to its use in the treatment of several diseases or to offer relief in processes that entail a certain type of malaise, and including its consideration as a means of relaxation and meditation. Although it was supposed that the roots of marijuana lay in Central America, it is now known that this is but an urban legend with little credibility and that its origins can be found recorded in Chinese medical references dating back to the year 2737 BC. Although this plant was not originally from Central America, it has aroused interest around the world, and above all in Mexico. It is in this country where the use of cannabis has gone from applications in textiles and medicine to its free sale, the bans on its use due to political and social pressures, its tolerance and, recently, its decriminalisation for recreational and medicinal use. Unfortunately there are few references on the history of this plant in Mexico, and thus we have considered it interesting to present some data about the generalities of marijuana, a brief history in the world, the development of decriminalisation in North America, its medicinal uses and its course through Mexico to the present day.

TITLE: Breve historia sobre la marihuana en Occidente.La marihuana es una sustancia con una extensa y controvertida historia. A lo largo del tiempo, esta planta, y desde hace mas de 5.000 años, ha sido utilizada para diferentes fines, que van desde el uso ludico y recreativo, pasando por un medio de relajacion y meditacion, hasta su uso en el tratamiento de varias enfermedades o el alivio de procesos vinculados a cierto tipo de malestares. Aunque se supuso que la marihuana tenia su origen en Mesoamerica, ahora se sabe que es solo una leyenda urbana de poca credibilidad y que sus origenes los podemos registrar en referencias medicas chinas datadas alrededor del año 2737 a. de C. Si bien esta planta no tiene un origen mesoamericano, si ha generado interes en el mundo, y sobre todo en Mexico. Es en este pais donde el uso del cannabis ha ido desde intereses textiles y medicinales hasta el consumo ludico, pasando por su venta libre, la prohibicion por presiones politicas y sociales, su tolerancia y, recientemente, su despenalizacion para uso ludico y medicinal. Desgraciadamente existen pocas referencias de la historia de esta planta en Mexico, por lo que ha sido de nuestro interes presentar algunos datos sobre las generalidades de la marihuana, una breve historia en el mundo, el desarrollo de la despenalizacion en Norteamerica, sus usos medicinales y su paso por Mexico hasta nuestros dias.

Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple Sclerosis: A Systematic Review and Meta-analysis.

Importance: Cannabinoids have antispastic and analgesic effects; however, their role in the treatment of multiple sclerosis (MS) symptoms is not well defined. Objective: To conduct a systematic review and meta-analysis to assess the efficacy and tolerability of medicinal cannabinoids compared with placebo in the symptomatic treatment of patients with MS. Data Sources: MEDLINE and the Cochrane Library Plus up to July 26, 2016. No restrictions were applied. The search was completed with information from ClinicalTrials.gov. Study Selection: Randomized, double-blind, and placebo-controlled trials evaluating the effect of medicinal cannabinoids by oral or oromucosal route of administration on the symptoms of spasticity, pain, or bladder dysfunction in adult patients with MS. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Effect sizes were calculated as standardized mean difference (SMD) for efficacy, and rate ratio (RR) for tolerability. Within each study, those SMDs evaluating the same outcome were combined before the meta-analysis to obtain a single value per outcome and study. Pooling of the studies was performed on an intention-to-treat basis by means of random-effect meta-analysis. Main Outcomes and Measures: Spasticity (on the Ashworth and Modified Ashworth scales and subjective), pain, bladder dysfunction, adverse events, and withdrawals due to adverse events. Results: Seventeen selected trials including 3161 patients were analyzed. Significant findings for the efficacy of cannabinoids vs placebo were SMD = -0.25 SD (95% CI, -0.38 to -0.13 SD) for spasticity (subjective patient assessment data), -0.17 SD (95% CI, -0.31 to -0.03 SD) for pain, and -0.11 SD (95% CI, -0.22 to -0.0008 SD) for bladder dysfunction. Results favored cannabinoids. Findings for tolerability were RR = 1.72 patient-years (95% CI, 1.46-2.02 patient-years) in the total adverse events analysis and 2.95 patient-years (95% CI, 2.14-4.07 patient-years) in withdrawals due to adverse events. Results described a higher risk for cannabinoids. The serious adverse events meta-analysis showed no statistical significance. Conclusions and Relevance: The results suggest a limited efficacy of cannabinoids for the treatment of spasticity, pain, and bladder dysfunction in patients with MS. Therapy using these drugs can be considered as safe. Trial Registration: PROSPERO Identifier: CRD42014015391.

Effects of the 2009 Medical Cannabinoid Legalization Policy on Hospital Use for Cannabinoid Dependency and Persistent Vomiting.

BACKGROUND & AIMS: In 2009, the U.S. Department of Justice issued a memo stating that it would not prosecute users and sellers who complied with the state laws allowing for medical use of marijuana. There are growing concerns about legalization of marijuana use and its related public health effects. We performed an interrupted time series analysis to evaluate these effects. METHODS: We collected a representative sample of hospital discharge data from the Healthcare Cost and Utilization Project, from January 1993 to December 2014. We divided the data in to 3 groups: the prelegalization period (1993-2008), the legalization period (2009), and the postlegalization period (2010-2014). The disease variables were International Classification of Disease-Ninth Revision-Clinical Modification 304.30 cannabinoid dependency unspecified (CDU), 536.2 persistent vomiting, and an aggregate of CDU and persistent vomiting. We performed interrupted time series and Poisson-Gamma regression analysis to calculate each year's incidence rate of unspecified and persistent vomiting and CDU per 100,000 hospital discharges. CDU, persistent vomiting, and aggregate of CDU and persistent vomiting were modeled separately to estimate average incidence rate ratio and 95% confidence interval for each study phase. RESULTS: We observed an increasing trend of CDU or an aggregate of CDU and persistent vomiting during the prelegalization period. The legalization of marijuana significantly increased the incidence rate during the legalization period (by 17.9%) and the yearly average increase in rate by 6% after policy implementation, compared to the prelegalization period. The increase in rate of persistent vomiting after policy implementation increased significantly (by about 8%), although there were no significant trends in increase prior to or during marijuana legalization in 2009. CONCLUSIONS: In an interrupted time series analysis of before, during, and after medical marijuana legalization, we estimated levels and rate changes in CDU and persistent vomiting. We found persistent increases in rates of CDU and persistent vomiting during and after legalization of marijuana.

Cannabinoides en pacientes con trastornos del espectro autista / Cannabinoids in patients with autism spectrum disorders

CONTEXTO CLÍNICO: Los trastornos del espectro autista (TEA) son un grupo de alteraciones o déficit del desarrollo de características crónicas y que afectan de manera distinta a cada paciente. Los TEA se definen como una disfunción neurológica crónica con fuerte base genética que desde edades tempranas se manifiesta en una serie de síntomas basados en la tríada de Wing que incluye: la comunicación, flexibilidad e imaginación; e interacción social. Dichas manifestaciones aparecen en la infancia con tendencia a persistir hasta la adolescencia y la edad adulta. En la mayoría de los casos se manifiestan en los primeros 5 años de vida.2,3 Se calcula que 1 de cada 160 niños tiene TEA, esta estimación representa una cifra media, ya que la prevalência observada varía considerablemente entre los distintos estudios indentificados. TECNOLOGÍA: La planta Cannabis sativa, habitualmente conocida como marihuana, contiene más de 500 compuestos. Los más abundantes son los de la familia de los cannabinoides. El componente psicoactivo principal de la marihuana es el cannabinoide ∆9-tetrahidrocannabinol (THC). El segundo compuesto más prevalente y más estudiado que presenta propiedades psicoactivas mínimas o ausentes, es el cannabidiol. Otros cannabinoidessin propiedades psicoactivas que han sido estudiados son el dronabinol y la nabilona. Para producirsus efectos, los cannabinoides activan los receptores del sistema endocannabinoide. Existen dos tipos principales de receptores en este sistema (CB1 y CB2). El receptor CB1 se ubica principalmente en el sistema nervioso central y el CB2 en las células inmunes. El sistema endocannabinoide puede tener un rol regulatorio de la excitación neuronal. OBJETIVO: Evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de cannabinoides para el tratamiento de pacientes con transtornos del espectro autista. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas (incluyendo Medline, Cochrane y CRD), en buscadores genéricos de Internet, agencias de evaluación de tecnologias sanitarias y financiadores de salud utilizando la siguiente estrategia:(Cannabis[Mesh] OR Medical Marijuana[Mesh] OR Endocannabinoids[Mesh] OR Cannabinoids[Mesh] OR Marijuana[tiab] OR Cannabi*[tiab] OR Dronabinol[tiab] OR Endocannabi*[tiab]) AND (AutismSpectrumDisorder[Mesh] OR AutisticDisorder[Mesh] OR Autism[tiab] OR Autistic*[tiab]). Para la selección de estudios se incluyeron sólo estudios primarios de cualquier diseño con um número de pacientes igual o superior a 10. Además se incluyeron evaluaciones de tecnologias sanitarias y económicas, guías de práctica clínica (GPC) y políticas de cobertura de otros sistemas de salud cuando estaban disponibles. RESULTADOS: No se hallaron estudios primarios que cumplan con los criterios establecidos. Sólo se encontro una evaluación de tecnología sanitaria (ETS). Una ETS realizada por la ANMAT en el año 2016 en Argentina, evaluó el uso de cannabinoides para el tratamiento de sujetos con TEA. Los autores concluyen que los estudios disponibles no aportan la evidencia suficiente que justifique el uso de los cannabinoides en el tratamiento del TEA. Se encontró un estudio en curso registrado en la base de datos de Ensayos Clínicos del Instituto Nacional de Salud de los Estados Unidos (ClinicalTrials.gov). Se trata de un ensayo clínico aleatorizado (ECA) doble ciego controlado con placebo, que se encuentra en etapa de reclutamiento de pacientes (NCT: 02956226). CONCLUSIONES: No se encontró evidencia científica disponible que permita establecer la efectividad del uso de cannabinoides para el tratamiento de pacientes con trastornos del espectro autista. Las guías de práctica clínica consultadas no hacen referencia a la utilización de esta tecnología para trastornos del espectro autista y no se identificaron políticas de cobertura que contemplen su uso.

Cannabinoides y dolor / Cannabinoids and pain

INTRODUCCIÓN: El dolor es una experiencia sensorial o emocional desagradable, asociada a daño tisular real o potencial, o bien descrita en términos de tal daño. El dolor tiene una alta prevalencia y un gran impacto individual, familiar, laboral, social y económico. El dolor crónico es una de las afecciones más incapacitantes y costosas en América del Norte, Europa y Australia. Las estimaciones de la prevalencia del dolor crónico, según los estudios evaluados, oscilan entre el 10,1% y el 55,2%. La OMS (Organización Mundial de la Salud) ha establecido la escalera terapéutica para el tratamiento del dolor, en la cual se identifica a los opiodes como la principal opción para el tratamiento del dolor asociado a cáncer moderado a severo, junto a otros no opioides y adyuvantes, según sea necesario. Las terapias complementarias aprobadas pueden incluir antiinflamatorios no esteroideos (AINEs), corticosteroides, anticonvulsivantes y antidepresivos. Una minoría de pacientes, entre el 10% y el 20%, siguen experimentando dolor significativo a pesar del adecuado tratamiento. Los cannabinoides han sido estudiados para el tratamiento del dolor y la espasticidad asociados a esclerosis múltiple, control de náuseas y vómitos, estimulación del apetito y analgesia. OBJETIVO: Evaluar la eficacia y seguridad de los cannabinoides en el tratamiento del dolor en pacientes de cualquier edad. MATERIALES Y MÉTODOS: Se llevó a cabo una búsqueda bibliográfica utilizando las siguientes palabras clave: cannabi* AND pain. Límites: seres humanos, revisiones sistemáticas, metaanálisis, ensayos clínicos, estudios publicados entre 2007-2017 en idioma inglés, español y alemán. Se exploraron bases de datos Cochrane Collaboration, PubMed, Biblioteca Virtual en Salud (BVS), Biblioteca Central de Medicina (RIMA), Epistemonikos, Tripdatabase, UNIVADIS, PROSPERO, Clinicaltrials.gov y búsqueda manual. Se incluyeron 24 estudios: 18 revisiones sistemáticas y 6 metaanálisis, publicados entre 2007 y 2017, con los siguientes puntos finales: reducción del dolor neuropático crónico, esclerosis múltiple (EM), fibromialgia, dolor asociado a cáncer, artritis reumatoidea (AR), dolor crónico no asociado a cáncer, dolor espinal crónico; tolerabilidad y seguridad. CONCLUSIONES: Los cannabinoides (nabilona, THC:CBD, THC) mostraron ser beneficiosos en el tratamiento del dolor crónico, cuando se los comparó con placebo. (CBD:cannabidiol). Los estudios que compararon los cannabinoides (nabilona) con dihidrocodeína o amitriptilina no mostraron diferencias entre ellos. Todas las dosis de THC demostraron efecto analgésico. El mayor alivio se consiguió con dosis altas (15-20 mg). El efecto analgésico del THC es comparable al obtenido con la codeína. El uso de cannabinoides permitió reducir la dosis de opiodes, como así también suspender otros esquemas terapéuticos adyuvantes como AINES, antidepresivos tricíclicos, dexametasona u ondansetrón. Se evidencia de esta manera el rol de los cannabinoides como tratamiento adyuvante para el dolor. El dronabinol demostró efectos mixtos (mejoría-empeoramiento) para el dolor. El nabiximols mostró beneficios para el tratamiento del dolor en pacientes con esclerosis múltiple. Los eventos adversos a corto plazo fueron leves. Con respecto a los eventos a largo plazo, principalmente observados con los productos que contienen THC, se describieron trastornos del espectro psicótico y síntomas maníacos. Los cannabinoides deben ser considerados como una opción terapéutica adyuvante en el tratamiento del dolor crónico.

Cannabinoides y epilepsia / Cannabinoids and epilepsy

INTRODUCCIÓN: La epilepsia afecta a alrededor de 65 millones de personas en el mundo, con una incidencia de 20-70 casos nuevos por 10.000 individuos por año. En la actualidad, existen múltiples tratamientos antiepilépticos, pero ninguno de ellos es curativo. El 30% de los pacientes son resistentes a los tratamientos antiepilépticos convencionales y presenta cuadros graves con mal pronóstico. En la actualidad, se observa una creciente presión por parte de los pacientes, familiares y de la sociedad en general para buscar alternativas terapéuticas no tradicionales para este tipo de cuadros, sumados a la información fácilmente accesible y al rol preponderante de las redes sociales y de los medios de comunicación. En este contexto, los cannabinoides se posicionan como una opción terapéutica a considerar en estos pacientes; ello obliga a analizar, desde una perspectiva científica, la evidencia disponible sobre efectividad y seguridad de la utilización terapéutica del cannabis o de sus derivados en el tratamiento de la epilepsia. Los dos principales cannabinoides biológicamente activos son el tetrahidrocannabinol (THC) y el cannabidiol (CBD). El THC es el compuesto psicoactivo más abundante en la planta, siendo el responsable de los cambios cognitivos y en la sensopercepción comúnmente asociados con el consumo de marihuana. La tolerancia y los efectos psicoactivos del THC son los factores críticos limitantes en el avance del potencial uso clínico del THC. El CBD posee baja afinidad por los receptores CB1 y CB2, actúa contrarrestando algunos efectos psicoactivos del THC y mejora su tolerabilidad. Presenta efecto anticonvulsivante, antiinflamatorio y antitumorigénico. Debido a la ausencia de propiedades psicoactivas, la baja tasa en la que se desarrolla tolerancia, su buen perfil de seguridad en humanos, así como su eficacia en los estudios preclínicos y algunos resultados alentadores en las fases clínicas, sugieren que podría ser un fármaco seguro y eficaz para el tratamiento de la epilepsia. OBJETIVO: Evaluar la eficacia y seguridad de los cannabinoides en el tratamiento de la epilepsia en pacientes de cualquier edad. MATERIAL Y METODO: Se llevó a cabo una búsqueda bibliográfica utilizando las siguientes palabras clave: cannabi* AND epilepsy y cannabinoids AND epilepsy. Límites: Seres humanos, sin restricción de lenguaje. Se exploraron bases de datos Cochrane Collaboration, PubMed, Biblioteca Virtual en Salud (BVS), Biblioteca Central de Medicina (RIMA), Epistemonikos, Tripdatabase, UNIVADIS, JAMA Network, Agencias de evaluación de tecnologías sanitarias, PROSPERO, Clinicaltrials.gov y búsqueda manual. Se incluyeron 10 estudios de 634 encontrados, publicados entre 1974 y 2016 (3 revisiones sistemáticas, 6 estudios descriptivos y un ensayo clínico controlado) con los siguientes puntos finales: reducción en la frecuencia de convulsiones (la cual fue definida en algunos estudios como proporción de pacientes libres de convulsiones durante 12 meses, o tres veces el intervalo más largo sin convulsiones y/o proporción de pacientes que presentan reducción del ≥50% en la frecuencia de las convulsiones durante el período de mantenimiento) y eventos adversos. CONCLUSIONES: El uso de CBD en formulaciones estandarizadas y controladas (obviamente, esto excluye a las preparaciones caseras), en una concentración del 99% y nunca menor al 96% con respecto al THC, como tratamiento adyuvante en la epilepsia refractaria o fármacorresistente en niños y jóvenes, ha demostrado tener efecto anticonvulsivante principalmente en crisis motoras y debe considerarse como una opción efectiva y segura en el tratamiento de este tipo de pacientes. Más allá de su probada eficacia anticonvulsivante, permite en la mayoría de los casos reducir la dosis de otros fármacos anticonvulsivantes y sus efectos adversos, lo que resulta en mejoría de la calidad de vida de los pacientes y de sus cuidadores. El uso medicinal de los cannabinoides y sus compuestos no adictivos deben ser considerados dentro del arsenal terapéutico de uso controlado, en el tratamiento de la epilepsia refractaria.

Usos terapéuticos de los cannabinoides / Therapeutic uses of cannabinoids

INTRODUCCIÓN: Este informe presenta los resultados obtenidos, respecto a la eficacia y seguridad del uso medicinal de los cannabinoides para el tratamiento del dolor crónico, náuseas y vómitos debido a quimioterapia, estimulación del apetito en infección HIV / SIDA, espasticidad debido a esclerosis múltiple o paraplejía, síndrome de Tourette y epilepsia refractaria a los tratamientos convencionales; en pacientes de cualquier edad. MÉTODO: Se seleccionaron 16 revisiones sistemáticas / metanálisis y 2 estudios observacionales. Muchos de los estudios que se incluyeron son de baja calidad metodológica, relativamente corto período de observación- con respecto a las patologías- y escaso número de pacientes para cada punto final aislado. Por lo tanto las conclusiones tienen significado clínico en cuanto a la dirección y tamaño del efecto benéfico pero nula significación estadística en algunas de las condiciones observadas. DOLOR: los canabinoides muestran beneficios leves a moderados para el tratamiento del dolor cuando se los compara con placebo. El THC fumado ha demostrado ser la intervención con mayor efectividad. El nivel de efectividad de los cannabinoides es dosis dependiente y resultan ser opciones muy útiles cuando se asocian a otras alternativas terapéuticas. EPILEPSIA REFRACTARIA: se observó una reducción mayor o igual al 50% en la frecuencia de las convulsiones en el 47% de los pacientes tratados con CBD o su asociación con THC. Puede ser considerada como una alternativa adyuvante en el tratamiento de estos pacientes. ESPASTICIDAD Y ESPASMOS DOLOROSOS EN EM: especialmente el nabiximols, podría tener un rol importante en el manejo de la espasticidad no controlada con las terapéuticas habituales. REDUCCIÓN DE NÁUSEAS Y VÓMITOS: fueron 4 veces más efectivos que el placebo para el control de nauseas y vómitos en pacientes bajo tratamiento quimioterápico. ESTIMULACIÓN DEL APETITO: el acetato de megestrol ha demostrado ser superior a los cannabinoides. REDUCCIÓN DE TICS EN EL SÍNDROME TOURETTE: sin conclusión. CONSIDERACIONES FINALES: Otros puntos finales: depresión, trastornos de ansiedad, trastornos del sueño, glaucoma, trastorno del humor, calidad de vida, ingesta calórica, aumento de peso; no existen evidencias sustentables para su aplicación en estas patologías. Los dos principales fitocannabinoides son: Delta-9-tetrahidrocannabinol (THC) el principal constituyente psicoactivo de la planta de marihuana y el cannabidiol (CBD) que tienen muy pocas propiedades psicoactivas y de interés creciente con respecto a su potencial terapéutico. Los sintéticos más usados son: nabilona; dronabinol; ácido ajulémico; nabiximols; levonantradol. CONCLUSIÓN: Los eventos adversos (EA) para todos los puntos finales demostraron un rango de intensidad leve a moderada. Los más frecuentes fueron: mareos, boca seca, náuseas, fatiga, somnolencia, respiratorios y gastrointestinales. No se demostró diferencias de EA entre los distintos tipos de cannabinoides. Todas las conclusiones son débiles en cuanto a la fuerza de la recomendación. Es muy importante la realización de estudios que cumplimenten todos los recaudos metodológicos y un adecuado tamaño muestral para avanzar en el conocimiento sobre el uso medicinal de los cannabinoides.

Cannabis use in people with severe mental illness: The association with physical and mental health--a cohort study. A Pharmacotherapy Monitoring and Outcome Survey study.

OBJECTIVE: In the general population cannabis use is associated with better cardiometabolic outcomes. Patients with severe mental illness frequently use cannabis, but also present increased cardiometabolic risk factors. We explore the association between cannabis use and cardiometabolic risk factors in patients with severe mental illness. METHOD: A total of 3169 patients with severe mental illness from a Dutch cohort were included in the study. The association of cannabis use with body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, glycated hemoglobin and Positive and Negative Syndrome Scale was examined with separate univariate AN(C)OVA. Changes in metabolic risk factors and Positive and Negative Syndrome Scale were examined after a follow-up interval of 9-24 months, for patients who continued, discontinued, started or were never using cannabis between the two assessments. RESULTS: Cannabis users at baseline had lower body mass index, smaller waist circumference, lower diastolic blood pressure, and more severe psychotic symptoms than non-users. Patients who discontinued their cannabis use after the first assessment had a greater increase in body mass index, waist circumference, diastolic blood pressure and triglyceride concentrations than other patients, and the severity of their psychotic symptoms had decreased more compared to continued users and non-users. CONCLUSION: Extra attention should be paid to the monitoring and treatment of metabolic parameters in patients who discontinue their cannabis use.