“Proceedings of an Almirall-sponsored satellite symposium held at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, 10 October 2018.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0048
“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from postapproval pragmatic studies. Postapproval studies have an essential role in demonstrating that an intervention is effective and well tolerated during use in daily clinical practice. Numerous large observational and registry studies of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray have been conducted subsequent to its approval in Europe in 2011. Collectively, these studies provide valuable insight into various aspects of THC:CBD spray during real-world use in patients with multiple sclerosis spasticity, including its long-term effectiveness and tolerability. The Italian Medicines Agency’s web-based registry is the largest observational study of THC:CBD oromucosal spray conducted to date, reporting on more than 1600 patients prescribed THC:CBD spray since it was introduced in Italy in 2013, and further supporting its effectiveness and tolerability profile.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0049
“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from randomized clinical trials. Subsequent to EMA approval of tetrahydrocannabinol (THC): cannabidiol (CBD) oromucosal spray based on results of various studies, including an enriched-design clinical trial, two newer postapproval randomized trials have confirmed its efficacy and safety for treating resistant multiple sclerosis spasticity, while simultaneously addressing specific authorities’ concerns. A double-blind, placebo-controlled, Phase IV trial, conducted as part of the EMA’s risk management plan, found no effect of THC:CBD spray on cognition and mood after 50 weeks of treatment. In the Sativex® as add-on therapy versus further optimized first-line ANTispastics (SAVANT) study, add-on THC:CBD spray was significantly more effective than readjusting standard antispasticity therapy and provided new evidence of efficacy as requested by German authorities. SAVANT results support practical recommendations for treating resistant multiple sclerosis spasticity in daily practice.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0050
“Cannabinoid-based interventions are being explored for central nervous system (CNS) pathologies such as neurodegeneration, demyelination, epilepsy, stroke, and trauma. As these disease states involve dysregulation of myelin integrity and/or remyelination, it is important to consider effects of the endocannabinoid system on oligodendrocytes and their precursors. In this review, we examine research reports on the effects of the endocannabinoid system (ECS) components on oligodendrocytes and their precursors, with a focus on therapeutic implications. Cannabinoid ligands and modulators of the endocannabinoid system promote cell signaling in oligodendrocyte precursor survival, proliferation, migration and differentiation, and mature oligodendrocyte survival and myelination. Agonist stimulation of oligodendrocyte precursor cells (OPCs) at both CB1 and CB2 receptors counter apoptotic processes via Akt/PI3K, and promote proliferation via Akt/mTOR and ERK pathways. CB1 receptors in radial glia promote proliferation and conversion to progenitors fated to become oligodendroglia, whereas CB2 receptors promote OPC migration in neonatal development. OPCs produce 2-arachidonoylglycerol (2-AG), stimulating cannabinoid receptor-mediated ERK pathways responsible for differentiation to arborized, myelin basic protein (MBP)-producing oligodendrocytes. In cell culture models of excitotoxicity, increased reactive oxygen species, and depolarization-dependent calcium influx, CB1 agonists improved viability of oligodendrocytes. In transient and permanent middle cerebral artery occlusion models of anoxic stroke, WIN55212-2 increased OPC proliferation and maturation to oligodendroglia, thereby reducing cerebral tissue damage. In several models of rodent encephalomyelitis, chronic treatment with cannabinoid agonists ameliorated the damage by promoting OPC survival and oligodendrocyte function. Pharmacotherapeutic strategies based upon ECS and oligodendrocyte production and survival should be considered.”