Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders. The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies. A systematic search was performed in PubMed, Embase and Cochrane library for articles published in English between January 1, 2000 and October 25, 2019. The search terms used were related to cannabis and CBD in adults. We identified 25 studies (927 patients; 538 men and 389 women), of which 22 studies were controlled clinical trials (833 patients) and three were observational designs (94 patients) from five countries. Formulations, dose and dosage schemes varied significantly between studies. Varying effects were identified from the randomized controlled trials (RCTs), more apparent effects from non-RCTs and minor safety issues in general. From the controlled trials, we identified anxiolytic effects with acute CBD administration, and therapeutic effects for social anxiety disorder, psychotic disorder and substance use disorders. In general, studies were heterogeneous and showed substantial risks of bias. Although promising results have been identified, considerable variation in dosage schemes and route of administration were employed across studies. There was evidence to support single dose positive effect on social anxiety disorder, short medium-term effects on symptomatic improvement in schizophrenia and lack of effect in the short medium-term on cognitive functioning in psychotic disorders. Overall, the administration was well tolerated with mild side effects.
BACKGROUND: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).
FINDINGS: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.
INTERPRETATION: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.
FUNDING: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.
OBJETIVOS: Es esencial comprender si el cannabidiol (CBD) es útil y seguro para el tratamiento de trastornos psiquiátricos para que los psiquiatras y los pacientes puedan tomar buenas decisiones clínicas. Nuestro objetivo era realizar una revisión sistemática con respecto a los beneficios y eventos adversos (AE) de CBD en el tratamiento de la esquizofrenia, trastornos psicóticos, trastornos de ansiedad, depresión, trastorno bipolar y trastornos por uso de sustancias. MÉTODOS: Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Scielo y Clinicaltrials.gov. Las pruebas se clasificaron de acuerdo con las normas de los grupos de trabajo de la WFSBP. RESULTADOS: La investigación bibliográfica arrojó 692 registros. Después del análisis, incluimos seis informes de casos y siete ensayos, que incluían 201 sujetos. La mayoría de los estudios publicados presentaron varios inconvenientes y no alcanzaron significación estadística. No hemos encontrado evidencia sobre trastornos depresivos y bipolares mayores. El nivel de evidencia para la retirada de cannabis es B; La adicción al cannabis es C2; El tratamiento de los síntomas positivos en la esquizofrenia y la ansiedad en el trastorno de ansiedad social es C1. Se notificaron casos discretos o no. Los EA más frecuentemente reportados son sedación y mareos. CONCLUSIÓN: La evidencia sobre la eficacia y la seguridad del CBD en psiquiatría es todavía escasa. Se necesitan ensayos controlados aleatorios más amplios y bien diseñados para evaluar los efectos del CBD en trastornos psiquiátricos.
AIMS: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of medical contexts.
METHODS: Publications involving administration of cannabidiol alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov.
RESULTS: A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. 23 studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 - 50 mg/Kg/day. Plasma concentrations were not provided in any publication. Cannabidiol was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of cannabidiol on reducing seizure frequency or severity (average 15 mg/Kg/day within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n=6-62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/Kg/day) were used in these studies.
CONCLUSION: This review highlights cannabidiol has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.
INTRODUCCIÓN: El cannabis está listado como una sustancia de la Lista I bajo la Ley de Sustancias Controladas de 1970, lo que significa que el gobierno federal de los Estados Unidos la define como una droga ilegal que tiene alto potencial de abuso y ningún uso médico establecido; Sin embargo, la mitad de los estados de la nación han promulgado leyes de "marihuana medicinal" (MM). Los médicos deben ser conscientes de las pruebas a favor y en contra del uso de MM en sus pacientes que pueden considerar el uso de esta sustancia. MÉTODOS: Se realizó una búsqueda en la base de datos de PubMed utilizando la cadena de texto: "Cannabis" [Mesh] O "Marijuana Abuse" [Mesh] O "Marijuana Médica" O "Marijuana Smoking" Tetrahidrocannabinol ". La búsqueda se limitó a las publicaciones de ensayos clínicos aleatorizados en inglés sobre sujetos humanos para identificar artículos sobre el uso terapéutico de los fito-canabinoides para trastornos psiquiátricos y neurológicos. Se excluyeron de la revisión los productos comercialmente disponibles (es decir, dronabinol, nabilona, nabiximoles) y cannabinoides sintéticos. Resultados Se identificaron publicaciones que incluían pacientes con demencia, esclerosis múltiple, enfermedad de Parkinson, enfermedad de Huntington, esquizofrenia, trastorno de ansiedad social, depresión, trastorno por uso de tabaco y dolor neuropático. DISCUSIÓN: Existe una gran variedad de condiciones médicas que son aprobadas para el tratamiento con MM para beneficio paliativo o terapéutico, dependiendo de la ley estatal. Es importante mantener un enfoque basado en evidencias en mente, incluso con sustancias consideradas ilegales bajo la ley federal de los Estados Unidos. Los médicos deben sopesar los riesgos y beneficios del uso de MM en sus pacientes y deben asegurarse de que los pacientes han probado otras modalidades de tratamiento con mayores niveles de evidencia para el uso cuando estén disponibles y sean apropiados.
The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.
En 2010, una revisión de Hazekamp y Grotenhermen abarcó los ensayos clínicos controlados de los años 2006-2009 sobre los medicamentos a base de cannabis, que siguieron el ejemplo de la revisión de Ben Amar (2006). La revisión actual informa sobre los datos clínicos más recientes disponibles de 2010-2014. Se realizó una búsqueda sistemática en la base de datos científica de PubMed, centrada en estudios clínicos que fueron aleatorizados, doble ciego y controlados con placebo. Las palabras clave utilizadas fueron cannabis, marijuana, marihuana, hachís, cannabinoides, tetrahidrocannabinol, THC, CBD, dronabinol, Marinol, nabilona, Cannador, nabiximoles y Sativex. Para la selección final, sólo se mantuvieron ensayos clínicos controlados adecuadamente. Se excluyeron los estudios abiertos, excepto si eran una continuación directa de un estudio discutido aquí. Se identificaron treinta y dos estudios controlados que evaluaron los efectos terapéuticos de los cannabinoides. Para cada ensayo clínico se describen el país donde se realizó el proyecto, el número de pacientes evaluados, el tipo de estudio y las comparaciones realizadas, los productos y las dosis utilizadas, su eficacia y sus efectos adversos. Sobre la base de los resultados clínicos, los cannabinoides presentan un potencial terapéutico interesante principalmente como analgésicos en el dolor neuropático crónico y espasticidad en la esclerosis múltiple. Pero una serie de otras indicaciones también parecen prometedoras. CBD (cannabidiol) emerge como otro valioso canabinoide para fines terapéuticos además de THC. Palabras clave: cannabinoides, cannabis, potencial terapéutico, ensayo clínico controlado, eficacia, seguridad, cannabidiol
Los trastornos de ansiedad son las enfermedades mentales más comunes que afectan a los seres humanos. Se extienden de pánico a los trastornos de ansiedad generalizada volcando el bienestar y el rendimiento psicosocial de los pacientes. Varios fármacos ansiolíticos convencionales están siendo utilizados que a su vez da lugar a varios efectos adversos. Por lo tanto, los estudios para encontrar medicamentos seguros adecuados a partir de fuentes naturales están siendo llevadas a cabo por los investigadores. El objetivo del presente estudio es el examen amplio de compuestos fitoquímicos con actividades ansiolíticas bien establecidos y sus relaciones estructura-actividad, así como los aspectos neuropsicofarmacológicos. Los resultados mostraron que los fitoquímicos como; alcaloides, flavonoides, ácidos fenólicos, lignanos, cinamatos, terpenos y saponinas poseen efectos ansiolíticos en una amplia gama de modelos animales de ansiedad. Los mecanismos implicados incluyen la interacción con los receptores de ácido γ-aminobutírico (GABA) A en la benzodiazepina (BZD) y los sitios no BZD con diversos afinidad a diferentes subunidades, serotoninérgicos 5-hydrodytryptamine (5-HT) 1A y 5-HT2A / receptores de C, sistemas noradrenérgicos y dopaminérgicos, los receptores de glicina y glutamato, y receptor κ-opioide, así como de cannabinoides (CB) 1 y CB2 receptores. Los fitoquímicos también modulan el eje hipotálamo-pituitario-adrenal (HPA), de los niveles de citoquinas pro-inflamatorias como la interleuquina (IL) -2, IL-6, IL-1β y el factor de necrosis tumoral (TNF) -α, y mejorar derivado del cerebro factor neurotrófico (BDNF) niveles. receptor de potencial transitorio canal catiónico subfamilia V (TRPV) 3, el óxido nítrico monofosfato de guanosina cíclico (GMPc-NO) de la vía y de la monoamina oxidasa enzimas son otros objetivos de fitoquímicos con actividad ansiolítica. Tomando en conjunto, estos fitoquímicos pueden ser considerados como suplementos a los tratamientos ansiolíticos convencionales con el fin de mejorar la eficacia y reducir los efectos adversos. Todavía se necesitan más estudios preclínicos y clínicos con el fin de reconocer las relaciones estructura-actividad, el metabolismo, absorción, y mecanismos neuropsicofarmacológicos de agentes naturales derivados de plantas.
La medicina en su continuo desarrollo se ha interesado por descubrir y utilizar substancias útiles para el cuerpo humano y el tratamiento de enfermedades. Desde hace años existe un debate en el campo de la ciencia en relación a la marihuana, el debate se sitúa entre quienes la consideran una planta con potenciales utilidades terapéuticas y quienes la consideran una droga de abuso. Método: Se revisaron 10 bases de datos con el fin de encontrar estudios clínicos con humanos, sobre los efectos de los aannabinoides, fitocannabinoides y cannabinoides sintéticos en distintas condiciones médicas. Resultados: 37 estudios fueron descritos, los estudios fueron analizados de acuerdo al país donde se realizaron, participantes, componentes y condición médica.
Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders. The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies. A systematic search was performed in PubMed, Embase and Cochrane library for articles published in English between January 1, 2000 and October 25, 2019. The search terms used were related to cannabis and CBD in adults. We identified 25 studies (927 patients; 538 men and 389 women), of which 22 studies were controlled clinical trials (833 patients) and three were observational designs (94 patients) from five countries. Formulations, dose and dosage schemes varied significantly between studies. Varying effects were identified from the randomized controlled trials (RCTs), more apparent effects from non-RCTs and minor safety issues in general. From the controlled trials, we identified anxiolytic effects with acute CBD administration, and therapeutic effects for social anxiety disorder, psychotic disorder and substance use disorders. In general, studies were heterogeneous and showed substantial risks of bias. Although promising results have been identified, considerable variation in dosage schemes and route of administration were employed across studies. There was evidence to support single dose positive effect on social anxiety disorder, short medium-term effects on symptomatic improvement in schizophrenia and lack of effect in the short medium-term on cognitive functioning in psychotic disorders. Overall, the administration was well tolerated with mild side effects.
