title: Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications.
abstract: Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain. jjfr@med.ucm.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. jjfr@med.ucm.es.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain. jjfr@med.ucm.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, 28040, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.affiliation: Servicio de Neonatología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martínez-Orgado
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D002186:Cannabinoids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D002186:Cannabinoids
keywords: CB1 and CB2 receptors; Cannabinoids; Endocannabinoid signaling system; FAAH and MAGL enzymes; Neurodegenerative disorders; Neuroprotection