“Cannabis extracts have been used for the treatment of epilepsy for centuries.
Yet, until recently, this empirical use was not linked to a known mechanism of action. Of the two main and most frequently investigated compounds derived from the cannabis plant, the mechanism of action of tetrahydrocannabinol (THC) is relatively clear and well documented (via CB1R distributed mainly centrally and CB2R distributed mainly peripherally).
The components of endocannabinoid system (ECS) are omnipresent in our bodies and have very divergent roles. Modulating ECS may have therapeutic potential in many human maladies, including psychiatric disorders (e.g., depression, posttraumatic stress disorder, anxiety, or schizophrenia), neurologic conditions, including epilepsy and neurodegenerative processes, diabetes and its complications, obesity, pain management, cancer treatment, graft versus host disease, treatment of chemotherapy side effects, and so on. The list is long, and it is constantly growing.
We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis.
This study provides unique evidence that the CB1R is dynamically and progressively involved from the start of mesial temporal lobe epileptogenesis.”
“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.”
.jpeg)
“Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options.