title: Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.
abstract: OBJECTIVE
  Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS). The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated. The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropic cannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.
  
  
  METHODS
  Experimental Autoimmune Encephalomyelitis (EAE) was induced by immunization with myelin oligodendroglial glycoprotein (MOG)35-55 peptide in mice. After immunization, mice were observed daily for signs of EAE and weight loss. Disease signs were evaluated using a standardized scoring system.
  
  
  RESULTS
  Immunohistochemical and Western blot assessments of key apoptotic markers reveal that CBD treatment is able to avoid Fas pathway activation, phospho-ERK p42/44 and cleaved caspase-3 triggering as well as alterations in mitochondrial permeability due to Bax/Bcl-2 unbalance. Moreover, CBD interferes with p53-p21 axis activation. As results, the absence of tissue apobody formation in spinal cord tissues of EAE-mice treated with CBD was established. Most of therapeutic properties of CS are currently ascribed to the psychotropic effects of phenylterpenoid delta-9 tetrahydrocannabinol.
  
  
  CONCLUSIONS
  We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.
authors.affiliation: Experimental Neurology Laboratory, IRCCS Centre Neurolesi "Bonino-Pulejo", Messina, Italy. emazzon.irccs@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Giacoppo
authors.forename: T
authors.initials: T
authors.lastname: Soundara Rajan
authors.forename: M
authors.initials: M
authors.lastname: Galuppo
authors.forename: F
authors.initials: F
authors.lastname: Pollastro
authors.forename: G
authors.initials: G
authors.lastname: Grassi
authors.forename: P
authors.initials: P
authors.lastname: Bramanti
authors.forename: E
authors.initials: E
authors.lastname: Mazzon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002188:Cannabis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010936:Plant Extracts; D002185:Cannabidiol