Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.
INTRODUCTION: : Nabiximols oromucosal spray, a cannabis-based medicine containing a balanced ratio of Δ-9-tetrahydrocannabinol and cannabidiol, is approved widely as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS). Most safety data for nabiximols derive from its use in MS spasticity, with some data available from the analgesia area.
AREAS COVERED: : This review compiles safety and tolerability data from all published observational studies, registry analyses and case reports identified in systematic searches in which nabiximols oromucosal spray was investigated for spasticity (n = 20) and/or chronic non-cancer pain (n = 4). Aligning with the known safety profile of nabiximols as demonstrated in randomised controlled trials, common adverse events reported consistently across studies conducted under clinical practice conditions were dizziness, fatigue and somnolence. The serious adverse events (SAE) rate with nabiximols in observational studies of MS spasticity was 3.1% (137/4351). A total of 39 treatment-related SAEs were reported in 32 patients with spasticity, all of which (where specified) were resolved. No treatment-related SAEs were recorded in studies of patients receiving nabiximols for pain.
EXPERT OPINION: : Real-world experience with nabiximols oromucosal spray in treating spasticity and chronic pain indicates that, overall, it is well tolerated and has a good safety profile.
Objective: To compile and synthesize the available literature describing medical cannabis use across various disease states. Data Sources: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Study Selection and Data Extraction: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. Data Synthesis: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. Relevance to Patient Care and Clinical Practice: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. Conclusions: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.
Background/purpose: Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability. Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies. Methods: A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria. Results: In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice. Conclusions: The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.
INTRODUCCIÓN: El uso de cannabis o cannabinoides para tratar condiciones médicas y / o aliviar síntomas es cada vez más frecuente. Sin embargo, el impacto de este uso en los resultados informados por los pacientes, como la calidad de vida relacionada con la salud (CVRS), sigue siendo poco claro. MÉTODOS: Realizamos una revisión sistemática y metanálisis, empleando directrices de Preferred Reporting Items for Systematic Reviews and Meta -Analyses (PRISMA). Se categorizaron los estudios basados en el diseño, la condición de enfermedad objetivo, y el tipo de cannabis o cannabinoide utilizado. Se realizaron estudios basados en la calidad y el riesgo de sesgo. Después de eliminar algunos estudios debido a la mala calidad o la insuficiencia de datos, realizamos meta-análisis de los estudios restantes basados en el diseño. Resultados: Veinte estudios cumplieron con nuestros criterios de selección predefinidos. Once estudios fueron ensayos controlados aleatorios (ECA, 2322 participantes); Los estudios restantes fueron de cohorte y diseño transversal. Los estudios de cannabinoides fueron en su mayoría ECA de mayor calidad de diseño que los estudios de cannabis, que utilizaron muestras auto-seleccionadas más pequeñas en estudios observacionales. Aunque no descubrimos una asociación significativa entre el cannabis y los cannabinoides para las condiciones médicas y la CVRS, algunos pacientes que los usaron para tratar el dolor, la esclerosis múltiple y los trastornos inflamatorios de la orilla han informado pequeñas mejoras en la CVRS, mientras que algunos pacientes con VIH han reportado una HRQoL reducida. CONCLUSIÓN: La relación entre la CVRS y el uso de cannabis o cannabinoides para condiciones médicas no es concluyente. Algunas poblaciones de pacientes informan mejoras, mientras que otras informan reducciones en la CVRS. Con el fin de informar a los usuarios, profesionales y formuladores de políticas más claramente, los estudios futuros deben cumplir con directrices de calidad de investigación más estrictas y más claramente informar los resultados de los pacientes.
Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.
