INTRODUCTION: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target.
METHODS: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS).
RESULTS: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).
CONCLUSIONS: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
OBJECTIVE: The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD.
METHODS: Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire.
RESULTS: Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P < 0.001). Analysis of specific motor symptoms revealed significant improvement after treatment in tremor (P < 0.001), rigidity (P = 0.004), and bradykinesia (P < 0.001).
CONCLUSIONS: There was also significant improvement of sleep and pain scores. No significant adverse effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.
WHAT IS KNOWN AND OBJECTIVE: Cannabidiol (CBD) is the main non-psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinson's disease.
CASES SUMMARY: Four patients treated with CBD had prompt and substantial reduction in the frequency of RBD-related events without side effects.
WHAT IS NEW AND CONCLUSION: This case series indicates that CBD is able to control the symptoms of RBD.
Background Cannabinoid are involved in Huntington's disease (HD) and cannabinoid stimulation improves the deficits in models of HD, suggesting promising effects in HD. Methods We conducted a double blind, cross over, placebocontrolled, phase II trial of SATIVEX∗ (a combination of plant extracts enriched in D9-tetrahydrocannabinol and cannabidiol) in patients with HD. SATIVEX and placebo were dispensed as an oral spray, up to 12 sprays/day. The primary end point was safety, evaluated as (a) absence of severe adverse events and (b) no greater deterioration of motor, cognitive, behavioural and functional UHDRS scales during the phase of active treatment. Secondary end points included the levels of neurotrophic factors, citokines, pro-and antiapoptotic proteins in blood and cerebrospinal fluid, the proteasome function, autophagy and resistance to neurotoxins in patients' fibroblasts. Results 26 patients were screened and 25 randomised. One patient withdrew the consent due to lack of improvement. 24 patients completed the trial. No serious adverse events were considered related to the medication. One patient developed anaemia related to gastrointestinal bleeding and got pregnant after completing the active treatment. Another patient had asymptomatic spinal fluid leucocytosis. The majority of the subjects reached the maximal recommended daily dose with good tolerance. Although still blinded, 19 patients had a differential score of more than 4 points in the Motor-UHDRS scale during the two trial phases. The sleep quality and anxiety improved in most patients in one phase of the trial. We obtained hundreds of aliquots of blood, lymphocytes, cerebrospinal fluid and fibroblasts for biomarker analysis. Conclusions The treatment with Sativex is safe for patients with HD and appears to have beneficial effects on patients symptoms. The significancy of these effects and the effects on biomarkers will be studied in the next months.
ANTECEDENTES: espasticidad muscular es común en la esclerosis múltiple (EM), que ocurre en más del 60% de los pacientes.
OBJETIVO: Comparar Sativex con el placebo en el alivio de los síntomas de la espasticidad en la EM.
MÉTODOS: A 15 semanas, multicéntrico, doble ciego, aleatorizado, controlado con placebo, de grupos paralelos en 337 sujetos con MS espasticidad no está completamente aliviado con la terapia anti-espasticidad actual.
RESULTADOS: El criterio de valoración principal fue una espasticidad 0-10 escala de calificación numérica (NRS). La intención de tratar (ITT) el análisis mostró una mejoría no significativa en la puntuación de NRS, a favor de Sativex. El por protocolo (PP) de la población (79% de los sujetos) cambio en NRS análisis de puntuación y de respuesta (> o = 30% de mejora respecto al valor basal) fueron significativamente superiores para Sativex, en comparación con el placebo: -1,3 frente a -0,8 puntos (cambio desde la línea de base, p = 0,035); y el 36% frente al 24% (respuesta, p = 0,040). Estos fueron apoyados por el tiempo hasta la respuesta (ITT: p = 0,068; PP: p = 0,025) analiza, cuidador impresión global de evaluación del cambio (p = 0,013) y la caminata cronometrada de 10 metros (p = 0,042). Entre los temas que lograron una respuesta> o = 30% en la espasticidad con Sativex, 98, 94 y 73% reportaron mejoras de 10, 20 y 30%, respectivamente, al menos una vez durante las primeras 4 semanas de tratamiento. Sativex fue generalmente bien tolerado, con la mayoría de los eventos adversos reportados ser de leve a moderada.
Discusión y conclusiones: el 0-10 NRS y el respondedor PP análisis demostraron que el tratamiento con Sativex resultó en una reducción significativa en la espasticidad resistente al tratamiento, en sujetos con avanzado MS y la espasticidad severa. La respuesta observada dentro de las primeras 4 semanas de tratamiento parece ser una ayuda útil para la predicción del estado de respondedor / no respondedor.
Estudio piloto de nabilona en la enfermedad de Huntington (HD). Doble ciego, controlado con placebo, estudio cruzado de nabilona frente a placebo. Resultado primario, Unified puntuación motora total de la enfermedad de Huntington Rating Scale (UHDRS). Las medidas secundarias: subsecciones UHDRS para la corea, la cognición y el comportamiento, y el inventario neuropsiquiátrico (NPI). 44 pacientes asignados al azar recibieron nabilona (1 o 2 mg), seguido de placebo (n = 22) o placebo seguido por nabilona (n = 22). El reclutamiento fue sencillo. La nabilona seguro y bien tolerado, sin episodios psicóticos. La evaluación de cualquiera de las dosis de nabilona versus placebo mostró una diferencia de tratamiento de 0,86 (IC del 95%: -1,8 a 3,52) para la puntuación total del motor; (IC del 95% 0.44 a la 2,92) 1,68 para la corea; (IC del 95%: -3,41 a 10,55) 3,57 para UHDRS la cognición; (IC del 95%: -0.11 a la 8.13) 4.01 para el comportamiento UHDRS, y 6,43 (IC del 95%: 0.2 a la 12.66) para la NPI. Grande ya ECA de nabilona en HD es factible y justificado.
The management of psychosis in Parkinson's disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson's Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.
ANTECEDENTES: El tratamiento a largo plazo de la enfermedad de Parkinson (EP) puede ser complicado por el desarrollo de la disquinesia inducida por levodopa. Datos del modelo clínicos y animales apoyan la opinión de que la modulación de la función de cannabinoides puede ejercer un efecto antidyskinetic. Los autores realizaron un estudio doble ciego, ensayo cruzado aleatorio controlado con placebo para examinar la hipótesis de que el cannabis puede tener un efecto beneficioso sobre la discinesia en la EP.
Métodos: Se realizó un estudio de 4 semanas de escalada de dosis para evaluar la seguridad y tolerabilidad de cannabis en seis PD pacientes con disquinesia inducida por levodopa. Luego se realizó un estudio cruzado controlado con placebo aleatorio (ECA), en la que 19 PD pacientes fueron aleatorizados para recibir el extracto de cannabis oral, seguido por placebo o viceversa. Cada fase de tratamiento se prolongó durante 4 semanas con una fase de lavado de 2 semanas intervenir. La medida de resultado primario fue un cambio en Unified Clasificación de Enfermedades Escala de Parkinson (UPDRS) (artículos 32 a 34) Puntuación discinesia. Las medidas de resultado secundarias incluyeron la escala Rush, escala Bain, tableta tarea de dibujo brazo y UPDRS puntuación total tras una entrada de la levodopa, así como las medidas de una actividad discinesia de la vida diaria (AVD) escala completado por el paciente, el PDQ-39, en diarios -off, y una gama de escalas categoría de calificación.
RESULTADOS: Diecisiete pacientes completaron el ECA. El cannabis fue bien tolerado, y no tenía ninguna acción pro- o antiparkinsonianos. No hubo pruebas de un efecto del tratamiento sobre la disquinesia inducida por levodopa según la evaluación de la UPDRS, o cualquiera de las medidas de resultado secundarias.
CONCLUSIONES: El extracto de cannabis administrado por vía oral resultó en ninguna mejoría objetiva o subjetiva en discinesias o parkinsonismo.
The neuropeptides neurokinin B, neurotensin, and anandamide, the endogenous ligands of NK3, NT1, and CB1 receptors respectively, are known to interact with brain dopaminergic transmission. This study evaluated the effects of these three antagonists of the NK3 (SR 142801), neurotensin (SR 48692), and cannabinoid (SR 141716) receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson disease. In this exploratory randomized, double-blind, placebo-controlled study, at the dose used, the drugs tested were well tolerated and could not improve parkinsonian motor disability.
Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target.
METHODS:
From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS).
RESULTS:
We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).
CONCLUSIONS:
Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
