Abstract:   Background: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numer- ous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory ac- tivities and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases.   Objective: The aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD...

Abstract Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the...

Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson's disease and Huntington's chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases...

Loss of cannabinoid receptors (CB1) occurs prior to neurodegeneration in Huntington’s disease (HD). The levels and distribution of CB1 RNA were equivalent in 3-week-old mice regardless of genotype demonstrating that the specific factors and appropriate chromatin structure that lead to the transcription of CB1 were present in the striatum of young R6/2 and R6/1 transgenic HD mice. The expression of the mutant HD transgene led progressively to decreased steadystate levels of CB1 mRNA in neurons of the lateral striatum, which was dependent on the size of the CAG repeat and relative expression of the gene encoding mutant huntingtin (HD). Although it is known that...

In order to investigate the sequence and pattern of neurodegeneration in Huntington’s disease, the distribution and density of cannabinoid CB1, dopamine D1 and D2, adenosine A2a and GABAA receptor changes were studied in the basal ganglia in early (grade 0), intermediate (grades 1, 2) and advanced (grade 3) neuropathological grades of Huntington’s disease. The results showed a sequential pattern of receptor changes in the basal ganglia with increasing neuropathological grades of Huntington’s disease. First, the very early stages of the disease (grade 0) were characterized by a major loss of cannabinoid CB1, dopamine D2 and adenosine A2a receptor binding in the caudate nucleus, putamen...