BACKGROUND: Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia.
OBJECTIVES: To determine the efficacy and safety of cannabinoids for the treatment of dementia.
SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates.
MAIN RESULTS: We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains. The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants). We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis. There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness.
AUTHORS' CONCLUSIONS: Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.
Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.
We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD] 0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65), appetite (SMD 0.81 95% CI: [-1.14, 2.75]; P = 0.42), nausea/vomiting (SMD 0.21 [-0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07), or sleep problems (SMD -0.09 95% CI: [-0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD 0.20 [-0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.
Resumen Antecedentes A la planta de cannabis y a los fármacos cannabinoides se les han atribuido efectos antiinflamatorios, analgésicos y anticonvulsivantes, entre otros, y por ello se han utilizado para tratar diversas patologías. Objetivo Evaluar el uso y los efectos terapéuticos de la planta de cannabis y los fármacos cannabinoides en diversas enfermedades. Método Se utilizó un diseño descriptivo mediante la revisión narrativa de la literatura sobre el uso de la planta de cannabis (mariguana) y los fármacos cannabinoides (nabilona, cannabinol y dronabinol, entre otros) en los buscadores Medline, Cochrane, SciELO y otros. Se incluyeron sólo los estudios clínicos, controlados, doble ciego y aleatorizados, así como la vía de administración y el fármaco cannabinoide utilizado. Resultados Treinta y cuatro estudios cumplieron con los criterios de inclusión. La nabilona fue el fármaco más empleado (12 estudios), seguida del delta-9-tetrahidrocannabinol (THC) (11 estudios). Tanto la planta como los fármacos cannabinoides se utilizaron para tratar diversos síntomas o enfermedades. Dos estudios reportaron su uso para el síndrome de Gilles de la Tourette. Discusión y conclusión La mayoría de los estudios revisados indican que la efectividad de la planta de mariguana o de los fármacos cannabinoides no es superior a la de los fármacos convencionales y que sus beneficios deben tomarse con cautela.
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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: Marijuana has been approved for a number of psychiatric conditions in many states in the US including posttraumatic stress disorder (PTSD), agitation in Alzheimer's disease, and Tourette's disorder. In this systematic review, we examine the strength of evidence for the efficacy of marijuana and other cannabinoids for these psychiatric indications.
DATA SOURCES: The literature (MEDLINE) was searched for studies published between January 1980 and March 2015 using search terms related to marijuana and other cannabinoids and the specific diagnosis.
STUDY SELECTION: The best quality of evidence, namely placebo-controlled, randomized clinical trials (RCTs) and meta-analyses, was sought per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the absence of RCTs, the next best available evidence (eg, observational studies, case reports) was reviewed. Of 170 publications that were screened, 40 were related to the topic, 29 were included in the qualitative synthesis, and 13 studies examined the efficacy of cannabinoids in humans.
DATA EXTRACTION: The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method.
RESULTS: No RCTs have thus far examined the efficacy of marijuana for Tourette's disorder, PTSD, or Alzheimer's disease. Lower-quality studies examined the efficacy of marijuana, Δ⁹-tetrahydrocannabinol, and nabilone; the strength of evidence for the use of cannabinoids for these conditions is very low at the present time. The consequences of chronic cannabinoid exposure includes tolerance, dependence, and withdrawal. Early and persistent marijuana use has been associated with the emergence of psychosis. Marijuana impairs attention, memory, IQ, and driving ability.
CONCLUSIONS: Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- or active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions. Physicians and policy-makers should take into account the limited existing evidence and balance that with side effects before approving medical marijuana for psychiatric indications.
Los cannabinoides tienen múltiples indicaciones médicas en cuidados paliativos, como alivio del dolor o náuseas o aumento del apetito y estabilización del peso. El valor de los cannabinoides para estas indicaciones no se resuelve suficientemente para los pacientes paliativos. Todavía no se ha realizado una revisión sistemática con metanálisis de la eficacia, tolerabilidad y seguridad basándose en estudios controlados aleatorios (ECA) o en estudios aleatorios de etiqueta abierta o cruzada. MATERIALES Y MÉTODOS: En las bases de datos del Registro Cochrane Central de Ensayos Controlados (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus y Clinicaltrials.gov, se realizó una extensa búsqueda de ECA, estudios aleatorios de etiqueta abierta o cruzado que trataron la cuestión subyacente. Abril de 2015. Se incluyeron en el análisis estudios con una duración de ≥ 2 semanas y ≥ 10 participantes por grupo de tratamiento. Utilizando un modelo de efectos aleatorios, se calcularon las estimaciones agrupadas de las tasas de eventos para los datos categóricos y las diferencias de medias estandarizadas (SMD) para las variables continuas y las diferencias de riesgo (RD) para las variables dicotómicas. RESULTADOS: Se incluyeron de los 108 estudios inicialmente 9, con un total de 1561 participantes que sufrían de enfermedades avanzadas o en fase terminal. La duración media de la investigación del cáncer fue de 8 semanas (16 días-11 semanas), de la investigación sobre el VIH 6 semanas (3-12 semanas) y del estudio se centró en el Alzheimer de 2 × 6 semanas. Los resultados de los resultados de cannabis / cannabinoides versus placebo en pacientes con cáncer no fueron significativos para la disminución del dolor de 30% (RD: 0,07, intervalo de confianza del 95%: 0,01 a 0,16, p = 0,07), ingesta calórica DMS: 0,2; IC del 95%: 0,66 a 1,06; p = 0,65) o problemas de sueño (DME: 0,09; IC del 95%: 0,62 a 0,43; p = 0,72). En el tratamiento del VIH, los cannabinoides fueron superiores al placebo para el resultado del cambio de peso (DME: 0,57; IC del 95%: 0,22-0,92; p = 0,001). El cambio en el apetito fue significativo para el tratamiento del VIH (DME: 0,57; IC del 95%: 0,11-1,03; p = 0,02), pero no para el tratamiento del cáncer (DME: 0,81; IC del 95%: 1,14 a 2,75; p = 0,42). Náusea / vómito (DMS: 0,20; IC del 95%: -0,03 a 0,44; p = 0,09) y calidad de vida relacionada con la salud (CVRS, DMS: 0,00, IC del 95%: 0,19 a 0,18, p = 0,98) Muestran diferencias significativas en la terapia de las dos enfermedades. Para los resultados de tolerabilidad los resultados no fueron significativos para la aparición de mareos (RD: 0,03; IC del 95%: 0,02 a 0,08; p = 0,23) o enfermedades psiquiátricas, como alucinaciones o psicosis (RD: - 0,01; IC del 95% : - 0,04 a 0,03, p = 0,69) en la terapia de cáncer. El resultado de las enfermedades psiquiátricas en el tratamiento del VIH fue significativo (RD: 0,05; IC del 95%: 0,00-0,11; p = 0,05). El número de retiros debido a eventos adversos como marcador de tolerabilidad y los informes de eventos adversos graves como medida de seguridad no fueron significativamente diferentes (RD: 1,20; IC del 95%: 0,85-1,71; p = 0,30 y DR: 1,15; IC del 95%: 0,88 - 1,49; p = 0,30, respectivamente). Dronabinol vs acetato de megestrol mostró una superioridad de megestrol en el tratamiento de la anorexia asociada al cáncer para el cambio de punto final del apetito (49 vs 75%, p = 0,0001), el aumento de peso (3 vs 11%, p = 0,02) HRQoL (p = 0,003) y tolerabilidad (p = 0,03). No hubo diferencias en la seguridad de las terapias (p = 0,12). En el tratamiento del síndrome de desgaste asociado al VIH, el acetato de megestrol fue mejor que el dronabinol para el criterio de valoración del aumento de peso (p = 0,0001), mientras que la tolerabilidad y la seguridad no difirieron. En la terapia de Alzheimer, el dronabinol fue mejor que el placebo en el punto final del aumento de peso según un estudio (n = 15). No se pudo encontrar una diferencia entre el cannabis herbario y los cannabinoides sintéticos, analizados por un estudio (n = 62). CONCLUSIÓN: Los cannabinoides pueden conducir a un aumento del apetito en pacientes con síndrome de emaciación del VIH, pero la terapia con acetato de megestrol es superior al tratamiento con cannabinoides. Los estudios incluidos no tuvieron una duración suficiente para responder a preguntas sobre la eficacia a largo plazo, la tolerabilidad y la seguridad de la terapia con cannabis o cannabinoides. Debido a la escasa cantidad de datos, no es posible recomendar un uso favorito de cannabis o cannabinoides en este momento.
Esta revisión sistemática tiene como objetivo integrar la evidencia sobre las indicaciones, eficacia, seguridad y farmacocinética de los cannabinoides médicos en sujetos de edad avanzada. La búsqueda bibliográfica se realizó utilizando PubMed, EMBASE, CINAHL y la Biblioteca Cochrane. Se seleccionaron ensayos controlados que incluían únicamente sujetos de edad avanzada (≥65 años) o que reportaban datos sobre subgrupos de edad avanzada. 105 (74%) documentos, de ensayos de intervención controlados, informaron la inclusión de sujetos de edad avanzada. Cinco estudios informaron datos de personas de edad avanzada separadamente. Estos eran ensayos controlados aleatorios, incluyendo en total 267 participantes (edad media 47 a 78 años). Las intervenciones fueron tetrahidrocannabinol oral (THC) (n=3) y THC oral combinado con cannabidiol (n = 2). Los estudios no mostraron eficacia en la discinesia, disnea ni náuseas y vómitos inducidos por quimioterapia. Dos estudios mostraron que el THC podría ser útil en el tratamiento de la anorexia y síntomas conductuales en la demencia. Los eventos adversos fueron más frecuentes durante el tratamiento con cannabinoides en comparación con el tratamiento control, y fueron más frecuentemente síntomas como sedación. Aunque los ensayos que estudiaban los cannabinoides médicos incluyeron sujetos de edad avanzada, hay una carencia de evidencia sobre su uso específicamente en pacientes de edad avanzada. Se necesitan ensayos impulsados adecuadamente para evaluar la eficacia y seguridad de los cannabinoides en sujetos de edad avanzada, ya que el potencial beneficio sintomático es especialmente atractivo en este grupo etario.
